We use cookies to improve your experience. By continuing to browse this site, you accept our cookie policy.×
Skip main navigation
Aging Health
Bioelectronics in Medicine
Biomarkers in Medicine
Breast Cancer Management
CNS Oncology
Colorectal Cancer
Concussion
Epigenomics
Future Cardiology
Future Medicine AI
Future Microbiology
Future Neurology
Future Oncology
Future Rare Diseases
Future Virology
Hepatic Oncology
HIV Therapy
Immunotherapy
International Journal of Endocrine Oncology
International Journal of Hematologic Oncology
Journal of 3D Printing in Medicine
Lung Cancer Management
Melanoma Management
Nanomedicine
Neurodegenerative Disease Management
Pain Management
Pediatric Health
Personalized Medicine
Pharmacogenomics
Regenerative Medicine
Published Online:https://doi.org/10.1517/14622416.6.2.115

ATP-binding cassette (ABC) genes play a role in the resistance of malignant cells to anticancer agents. The ABC gene products, including ABCB1 (P-glycoprotein) and ABCG2 (breast cancer-resistance protein [BCRP], mitoxantrone-resistance protein [MXR], or ABC transporter in placenta [ABCP]), are also known to influence oral absorption and disposition of a wide variety of drugs. As a result, the expression levels of these proteins in humans have important consequences for an individual’s susceptibility to certain drug-induced side effects, interactions, and treatment efficacy. Naturally occurring variants in ABC transporter genes have been identified that might affect the function and expression of the protein. This review focuses on recent advances in the pharmacogenetics of the ABC transporters ABCB1 and ABCG2, and discusses potential implications of genetic variants for the chemotherapeutic treatment of cancer.

Papers of special note have been highlighted as either of interest (•) or of considerable interest (••) to readers.

Bibliography

  • 1 Litman T, Druley TE, Stein WD, Bates SE: From MDR to MXR: new understanding of multidrug resistance systems, their properties and clinical significance. Cell. Mol. Life Sci.58,931959 (2001).
  • 2 Borst P, Evers R, Kool M, Wijnholds J: A family of drug transporters: the multidrug resistance-associated proteins. J. Natl Cancer Inst.92,12951302 (2000).
  • 3 Dean M, Rzhetsky A, Allikmets R: The human ATP-binding cassette (ABC) transporter superfamily. Genome Res.1111561166 (2001).
  • 4 Gottesman MM, Ambudkar SV: Overview: ABC transporters and human disease. J. Bioenerg. Biomembr.33,453458 (2001).
  • 5 Lin JH, Yamazaki M: Role of P-glycoprotein in pharmacokinetics: clinical implications. Clin. Pharmacokinet.42,5998 (2003).
  • 6 Schinkel AH, Smit JJ, van Tellingen O et al.: Disruption of the mouse mdr1a P-glycoprotein gene leads to a deficiency in the blood-brain barrier and to increased sensitivity to drugs. Cell77,491502 (1994).•• Demonstrates the impact of ABCB1 on the pharmacokinetics and toxicity of substrate drugs.
  • 7 Schinkel AH, Mayer U, Wagenaar E et al.: Normal viability and altered pharmacokinetics in mice lacking mdr1-type (drug-transporting) P-glycoproteins. Proc. Natl Acad. Sci. USA94,40284033 (1997).
  • 8 Jonker JW, Buitelaar M, Wagenaar E et al.: The breast cancer resistance protein protects against a major chlorophyll-derived dietary phototoxin and protoporphyria. Proc. Natl Acad. Sci. USA99,1564915654 (2002).
  • 9 Sparreboom A, van Asperen J, Mayer U et al.: Limited oral bioavailability and active epithelial excretion of paclitaxel (Taxol) caused by P-glycoprotein in the intestine. Proc. Natl Acad. Sci. USA94,20312035 (1997).
  • 10 Smit JW, Huisman MT, van Tellingen O, Wiltshire HR, Schinkel AH: Absence or pharmacological blocking of placental P-glycoprotein profoundly increases fetal drug exposure. J. Clin. Invest.104,14411447 (1999).
  • 11 Wijnholds J, deLange EC, Scheffer GL et al.: Multidrug resistance protein 1 protects the choroid plexus epithelium and contributes to the blood-cerebrospinal fluid barrier. J. Clin. Invest.105,279285 (2000).
  • 12 Rao VV, Dahlheimer JL, Bardgett ME et al.: Choroid plexus epithelial expression of MDR1 P glycoprotein and multidrug resistance-associated protein contribute to the blood-cerebrospinal-fluid drug-permeability barrier. Proc. Natl Acad. Sci. USA96,39003905 (1999).
  • 13 Fromm MF: The influence of MDR1 polymorphisms on P-glycoprotein expression and function in humans. Adv. Drug Deliv. Rev.54,12951310 (2002).
  • 14 Lockhart AC, Tirona RG, Kim RB: Pharmacogenetics of ATP-binding cassette transporters in cancer and chemotherapy. Mol. Cancer Ther.2,685698 (2003).
  • 15 Marzolini C, Paus E, Buclin T, Kim RB: Polymorphisms in human MDR1 (P-glycoprotein): recent advances and clinical relevance. Clin. Pharmacol. Ther.75, 1333 (2004).• Recent review outlining the potential clinical importance of ABCB1.
  • 16 Hyde SC, Emsley P, Hartshorn MJ et al.: Structural model of ATP-binding proteins associated with cystic fibrosis, multidrug resistance and bacterial transport. Nature346,362365 (1990).
  • 17 Leabman MK, Huang CC, DeYoung J et al.: Natural variation in human membrane transporter genes reveals evolutionary and functional constraints. Proc. Natl Acad. Sci. USA100,58965901 (2003).
  • 18 Cotton RGH, Horaitis O: The HUGO mutation database initiative. Pharmacogenomics J.2,1619 (2002).
  • 19 Allen JD, Brinkhuis RF, Wijnholds J, Schinkel AH: The mouse Bcrp1/Mxr/Abcp gene: amplification and overexpression in cell lines selected for resistance to topotecan, mitoxantrone, or doxorubicin. Cancer Res.59,42374241 (1999).
  • 20 Sparreboom A, Nooter K: Does P-glycoprotein play a role in anticancer drug pharmacokinetics? Drug Resist. Updat.3, 357363 (2000).
  • 21 Gottesman MM, Fojo T, Bates SE: Multidrug resistance in cancer: role of ATP-dependent transporters. Nat. Rev. Cancer2, 4858 (2002).
  • 22 Baer MR, George SL, Dodge RK et al.: Phase III study of the multidrug resistance modulator PSC-833 in previously untreated patients 60 years of age and older with acute myeloid leukemia: Cancer and Leukemia Group B Study 9720. Blood 100,12241232 (2002).
  • 23 Gottesman MM, Pastan I: Biochemistry of multidrug resistance mediated by the multidrug transporter. Ann. Rev. Biochem.62,385427 (1993).
  • 24 Ambudkar SV, Dey S, Hrycyna CA, Ramachandra M, Pastan I, Gottesman MM: Biochemical, cellular, and pharmacological aspects of the multidrug transporter. Ann. Rev. Pharmacol. Toxicol.39,361398 (1999).
  • 25 van Tellingen O: The importance of drug-transporting P-glycoproteins in toxicology. Toxicol. Lett.120,3141 (2001).
  • 26 van Asperen J, Van Tellingen O, Beijnen JH: The pharmacological role of P-glycoprotein in the intestinal epithelium. Pharmacol. Res.37,429435 (1998).
  • 27 Schinkel AH: The physiological function of drug-transporting P-glycoproteins. Semin. Cancer Biol.8,161170 (1997).
  • 28 Schellens JH, Malingre MM, Kruijtzer CM et al.: Modulation of oral bioavailability of anticancer drugs: from mouse to man. Eur. J. Pharm. Sci.12,103110 (2000).
  • 29 Chaudhary PM, Roninson IB: Expression and activity of P-glycoprotein, a multidrug efflux pump, in human hematopoietic stem cells. Cell66,8594 (1991).
  • 30 Chaudhary PM, Mechetner EB, Roninson IB: Expression and activity of the multidrug resistance P-glycoprotein in human peripheral blood lymphocytes. Blood80, 27352739 (1992).
  • 31 Randolph GJ, Beaulieu S, Pope M et al.: A physiologic function for P-glycoprotein (MDR-1) during the migration of dendritic cells from skin via afferent lymphatic vessels. Proc. Natl Acad. Sci. USA95,69246929 (1998).
  • 32 Malingre MM, Beijnen JH, Schellens JH: Oral delivery of taxanes. Invest. New Drugs19,155162 (2001).
  • 33 Malingre MM, Richel DJ, Beijnen JH et al.: Coadministration of cyclosporine strongly enhances the oral bioavailability of docetaxel. J. Clin. Oncol.19,11601166 (2001).
  • 34 Meerum Terwogt JM, Malingre MM, Beijnen JH et al.: Coadministration of oral cyclosporin A enables oral therapy with paclitaxel. Clin. Cancer Res.5,3379–3384 (1999).
  • 35 Bailey-Dell KJ, Hassel B, Doyle LA, Ross DD: Promoter characterization and genomic organization of the human breast cancer resistance protein (ATP-binding cassette transporter G2) gene. Biochim. Biophys. Acta1520, 234–241 (2001).
  • 36 Bates SE, Robey R, Miyake K, Rao K, Ross DD, Litman T: The role of half-transporters in multidrug resistance. J. Bioenerg. Biomembr.33,503511 (2001).
  • 37 Leonard GD, Polgar O, Bates SE: ABC transporters and inhibitors: new targets, new agents. Curr. Opin. Investig. Drugs 3,16521659 (2002).
  • 38 Leonard GD, Fojo T, Bates SE: The role of ABC transporters in clinical practice. Oncologist8,411424 (2003).
  • 39 Allikmets R, Schriml LM, Hutchinson A, Romano-Spica V, Dean M: A human placenta-specific ATP-binding cassette gene (ABCP) on chromosome 4q22 that is involved in multidrug resistance. Cancer Res.58,53375339 (1998).•• First identification of ABCG2.
  • 40 Doyle LA, Yang W, Abruzzo LV et al.: A multidrug resistance transporter from human MCF-7 breast cancer cells. Proc. Natl Acad. Sci. USA95,1566515670 (1998).
  • 41 Miyake K, Mickley L, Litman T et al.: Molecular cloning of cDNAs which are highly overexpressed in mitoxantrone-resistant cells: demonstration of homology to ABC transport genes. Cancer Res.59,813 (1999).
  • 42 Allen JD, Schinkel AH: Multidrug resistance and pharmacological protection mediated by the breast cancer resistance protein (BCRP/ABCG2). Mol. Cancer Ther.1,427434 (2002).
  • 43 Ross DD, Yang W, Abruzzo LV et al.: Atypical multidrug resistance: breast cancer resistance protein messenger RNA expression in mitoxantrone-selected cell lines. J. Natl Cancer Inst.91,429433 (1999).
  • 44 Xu J, Liu Y, Yang Y, Bates S, Zhang JT: Characterization of oligomeric human half ABC transporter ABCG2/BCRP/MXR/ABCP in plasma membranes. J. Biol. Chem. 279, 19781–19789 (2004).
  • 45 Zhou S, Morris JJ, Barnes Y, Lan L, Schuetz JD, Sorrentino BP: Bcrp1 gene expression is required for normal numbers of side population stem cells in mice, and confers relative protection to mitoxantrone in hematopoietic cells in vivo. Proc. Natl Acad. Sci. USA99, 12339–12344 (2002).
  • 46 Zhou S, Schuetz JD, Bunting KD et al.: The ABC transporter Bcrp1/ABCG2 is expressed in a wide variety of stem cells and is a molecular determinant of the side-population phenotype. Nat. Med. 7,10281034 (2001).
  • 47 Zhou S, Zong Y, Lu T, Sorrentino BP: Hematopoietic cells from mice that are deficient in both Bcrp1/Abcg2 and Mdr1a/1b develop normally but are sensitized to mitoxantrone. Biotechniques35,12481252 (2003).
  • 48 Robey RW, Honjo Y, van de Laar A et al.: A functional assay for detection of the mitoxantrone resistance protein, MXR (ABCG2). Biochim. Biophys. Acta1512, 171182 (2001).
  • 49 Krishnamurthy P, Ross DD, Nakanishi T et al.: The stem cell marker Bcrp/ABCG2 enhances hypoxic cell survival through interactions with heme. J. Biol. Chem.279, 24218–24225 (2004).
  • 50 Kolwankar D, Glover DD, Ware JA, Tracy TS: Expression and function of ABCB1 and ABCG2 in human placental tissue. Drug Metab. Dispos. (2005) (In Press).
  • 51 Jonker JW, Smit JW, Brinkhuis RF et al.: Role of breast cancer resistance protein in the bioavailability and fetal penetration of topotecan. J. Natl Cancer Inst. 92, 1651–1656 (2000).•• Demonstrates the impact of ABCG2 on oral drug absorption.
  • 52 Han B, Zhang JT: Multidrug resistance in cancer chemotherapy and xenobiotic protection mediated by the half ATP-binding cassette transporter ABCG2. Curr. Med. Chem. Anti-Canc. Agents4,3142 (2004).
  • 53 Maliepaard M, Scheffer GL, Faneyte IF et al.: Subcellular localization and distribution of the breast cancer resistance protein transporter in normal human tissues. Cancer Res.61,34583464 (2001).
  • 54 Allen JD, van Loevezijn A, Lakhai JM et al.: Potent and specific inhibition of the breast cancer resistance protein multidrug transporter in vitro and in mouse intestine by a novel analogue of fumitremorgin C. Mol. Cancer Ther.1,417425 (2002).
  • 55 van Herwaarden AE, Jonker JW, Wagenaar E et al.: The breast cancer resistance protein (Bcrp1/Abcg2) restricts exposure to the dietary carcinogen 2-amino-1-methyl-6-phenylimidazo[4,5-b]pyridine. Cancer Res.63,64476452 (2003).
  • 56 Ejendal KF, Hrycyna CA: Multidrug resistance and cancer: the role of the human ABC transporter ABCG2. Curr. Protein Pept. Sci.3,503511 (2002).
  • 57 Kruijtzer CM, Beijnen JH, Rosing H et al.: Increased oral bioavailability of topotecan in combination with the breast cancer resistance protein and P-glycoprotein inhibitor GF120918. J. Clin. Oncol.20, 29432950 (2002).• Describes dual modulation of ABCB1 and ABCB2 function in humans by a potent inhibitor.
  • 58 Kruijtzer CM, Beijnen JH, Schellens JH: Improvement of oral drug treatment by temporary inhibition of drug transporters and/or cytochrome P450 in the gastrointestinal tract and liver: an overview. Oncologist7,516530 (2002).
  • 59 Allen JD, Brinkhuis RF, van Deemter L, Wijnholds J, Schinkel AH: Extensive contribution of the multidrug transporters P-glycoprotein and Mrp1 to basal drug resistance. Cancer Res.60,57615766 (2000).
  • 60 de Bruin M, Miyake K, Litman T, Robey R, Bates SE: Reversal of resistance by GF120918 in cell lines expressing the ABC half-transporter, MXR. Cancer Lett.146, 117126 (1999).
  • 61 Rabindran SK, He H, Singh M et al.: Reversal of a novel multidrug resistance mechanism in human colon carcinoma cells by fumitremorgin C. Cancer Res.58,58505858 (1998).
  • 62 Rabindran SK, Ross DD, Doyle LA, Yang W, Greenberger LM: Fumitremorgin C reverses multidrug resistance in cells transfected with the breast cancer resistance protein. Cancer Res.60, 47–50 (2000).
  • 63 Imai Y, Asada S, Tsukahara S, Ishikawa E, Tsuruo T, Sugimoto Y: Breast cancer resistance protein exports sulfated estrogens but not free estrogens. Mol. Pharmacol.64, 610–618 (2003).
  • 64 Imai Y, Tsukahara S, Ishikawa E, Tsuruo T, Sugimoto Y: Estrone and 17β-estradiol reverse breast cancer resistance protein- mediated multidrug resistance. Jpn. J. Cancer Res.93,231235 (2002).
  • 65 Ee PL, Kamalakaran S, Tonetti D, He X, Ross DD, Beck WT: Identification of a novel estrogen response element in the breast cancer resistance protein (ABCG2) gene. Cancer Res.64,12471251 (2004).
  • 66 Janvilisri T, Venter H, Shahi S, Reuter G, Balakrishnan L, van Veen HW: Sterol transport by the human breast cancer resistance protein (ABCG2) expressed in Lactococcus lactis. J. Biol. Chem.278, 2064520651 (2003).
  • 67 Ramachandra M, Ambudkar SV, Gottesman MM, Pastan I, Hrycyna CA: Functional characterization of a glycine 185-to-valine substitution in human P-glycoprotein by using a vaccinia-based transient expression system. Mol. Biol. Cell7,14851498 (1996).
  • 68 Hoffmeyer S, Burk O, von Richter O et al.: Functional polymorphisms of the human multidrug-resistance gene: multiple sequence variations and correlation of one allele with P-glycoprotein expression and activity in vivo. Proc. Natl Acad. Sci. USA97,34733478 (2000).•• Describes the first systematic screen for variants in the human ABCB1.
  • 69 Hoffmeyer S, Brinkmann U, Cascorbi I: Frequency of single nucleotide polymorphisms in the P-glycoprotein drug transporter MDR1 gene in white subjects. Pharmacogenomics2,5164 (2001).
  • 70 Saito S, Iida A, Sekine A et al.: Three hundred twenty-six genetic variations in genes encoding nine members of ATP-binding cassette, subfamily B (ABCB/MDR/TAP), in the Japanese population. J. Hum. Genet.47,3850 (2002).
  • 71 Schwab M, Eichelbaum M, Fromm MF: Genetic polymorphisms of the human mdr1 drug transporter. Ann. Rev. Pharmacol. Toxicol.43,285307 (2003).
  • 72 Evans WE, McLeod HL: Pharmacogenomics – drug disposition, drug targets, and side effects. N. Engl. J. Med.348,538549 (2003).
  • 73 Kroetz DL, Pauli-Magnus C, Hodges LM et al.: Sequence diversity and haplotype structure in the human ABCB1 (MDR1, multidrug resistance transporter) gene. Pharmacogenetics13,481494 (2003).•• Description of the haplotype structure of the human ABCB1.
  • 74 Kimchi-Sarfaty C, Gribar JJ, Gottesman MM: Functional characterization of coding polymorphisms in the human MDR1 gene using a vaccinia virus expression system. Mol. Pharmacol.62, 16 (2002).
  • 75 Mickley LA, Lee JS, Weng Z et al.: Genetic polymorphism in MDR-1: a tool for examining allelic expression in normal cells, unselected and drug-selected cell lines, and human tumors. Blood91,17491756 (1998).
  • 76 Kim RB, Leake BF, Choo EF et al.: Identification of functionally variant MDR1 alleles among European Americans and African Americans. Clin. Pharmacol. Ther.70,189199 (2001).
  • 77 Greiner B, Eichelbaum M, Fritz P et al.: The role of intestinal P-glycoprotein in the interaction of digoxin and rifampin. J. Clin. Invest.104,147153 (1999).
  • 78 Hitzl M, Drescher S, van der Kuip H et al.: The C3435T mutation in the human MDR1 gene is associated with altered efflux of the P-glycoprotein substrate rhodamine 123 from CD56+ natural killer cells. Pharmacogenetics11,293298 (2001).
  • 79 Song X, Xie M, Zhang H, Li Y, Sachdeva K, Yan B: The pregnane X receptor binds to response elements in a genomic context-dependent manner, and PXR activator rifampicin selectively alters the binding among target genes. Drug Metab. Dispos.32, 3542 (2004).
  • 80 Owen A, Chandler B, Back DJ, Khoo SH: Expression of pregnane-X-receptor transcript in peripheral blood mononuclear cells and correlation with MDR1 mRNA. Antivir. Ther.9,819821 (2004).
  • 81 Takane H, Kobayashi D, Hirota T et al.: Haplotype-oriented genetic analysis and functional assessment of promoter variants in the MDR1 (ABCB1) gene. J. Pharmacol. Exp. Ther.311,11791187 (2004).
  • 82 Kerb R, Hoffmeyer S, Brinkmann U: ABC drug transporters: hereditary polymorphisms and pharmacological impact in MDR1, MRP1 and MRP2. Pharmacogenomics2, 51–64 (2001).
  • 83 Honjo Y, Morisaki K, Huff LM et al.: Single-nucleotide polymorphism (SNP) analysis in the ABC half-transporter ABCG2 (MXR/BCRP/ABCP1). Cancer Biol. Ther.1, 696–702 (2002).
  • 84 Iida A, Saito S, Sekine A et al.: Catalog of 605 single-nucleotide polymorphisms (SNPs) among 13 genes encoding human ATP-binding cassette transporters: ABCA4, ABCA7, ABCA8, ABCD1, ABCD3, ABCD4, ABCE1, ABCF1, ABCG1, ABCG2, ABCG4, ABCG5, and ABCG8. J. Hum. Genet.47,285310 (2002).
  • 85 Imai Y, Nakane M, Kage K et al.: C421A polymorphism in the human breast cancer resistance protein gene is associated with low expression of Q141K protein and low-level drug resistance. Mol. Cancer Ther.1,611616 (2002).
  • 86 Zamber CP, Lamba JK, Yasuda K et al.: Natural allelic variants of breast cancer resistance protein (BCRP) and their relationship to BCRP expression in human intestine. Pharmacogenetics13,1928 (2003).• Evaluation of ethnic variation in frequency of ABCG2 SNPs.
  • 87 de Jong FA, Marsh S, Mathijssen RH et al.: ABCG2 pharmacogenetics: ethnic differences in allele frequency and assessment of influence on irinotecan disposition. Clin. Cancer Res. 10,58895894 (2004).
  • 88 Backstrom G, Taipalensuu J, Melhus H et al.: Genetic variation in the ATP-binding cassette transporter gene ABCG2 (BCRP) in a Swedish population. Eur. J. Pharm. Sci.18, 359364 (2003).
  • 89 Mizuarai S, Aozasa N, Kotani H: Single nucleotide polymorphisms result in impaired membrane localization and reduced ATPase activity in multidrug transporter ABCG2. Int. J. Cancer109, 238246 (2004).
  • 90 Itoda M, Saito Y, Shirao K et al.: Eight novel single nucleotide polymorphisms in ABCG2/BCRP in Japanese cancer patients administered irinotacan. Drug Metab. Pharmacokinet.18,212217 (2003).
  • 91 Gelderblom H, Loos WJ, Sissung TM et al.: Effect of ABCG2 genotype and intestinal mRNA expression on the bioavailability of topotecan. Proc. Am. Soc. Clin. Oncol.22 (2004).
  • 92 Kondo C, Suzuki H, Itoda M et al.: Functional analysis of SNPs variants of BCRP/ABCG2. Pharm. Res.21,18951903 (2004).
  • 93 Kobayashi D, Ieiri I, Hirota T et al.: Functional assessment of abcg2 (bcrp) gene polymorphisms to protein expression in human placenta. Drug Metab. Dispos.33, 94101 (2005).
  • 94 Morisaki K, Robey RW, Nadjem T et al.: The Q141K single-nucleotide polymorphism impacts the transporter activity of ABCG2. Proc. Am. Assoc. Cancer Res.45,2463 (2004).
  • 95 Allen JD, Jackson SC, Schinkel AH: A mutation hot spot in the Bcrp1 (Abcg2) multidrug transporter in mouse cell lines selected for doxorubicin resistance. Cancer Res.62,22942299 (2002).
  • 96 Honjo Y, Hrycyna CA, Yan QW et al.: Acquired mutations in the MXR/BCRP/ABCP gene alter substrate specificity in MXR/BCRP/ABCP-overexpressing cells. Cancer Res. 61,66356639 (2001).
  • 97 Robey RW, Honjo Y, Morisaki K et al.: Mutations at amino-acid 482 in the ABCG2 gene affect substrate and antagonist specificity. Br. J. Cancer89,1971–1978 (2003).
  • 98 Robey RW, Steadman K, Polgar O et al.: Pheophorbide a is a specific probe for ABCG2 function and inhibition. Cancer Res. 64,12421246 (2004).
  • 99 Mitomo H, Kato R, Ito A et al.: A functional study on polymorphism of the ATP-binding cassette transporter ABCG2: critical role of arginine-482 in methotrexate transport. Biochem. J.373,767774 (2003).
  • 100 Volk EL, Schneider E: Wild-type breast cancer resistance protein (BCRP/ABCG2) is a methotrexate polyglutamate transporter. Cancer Res.63,55385543 (2003).
  • 101 Kurata Y, Ieiri I, Kimura M et al.: Role of human MDR1 gene polymorphism in bioavailability and interaction of digoxin, a substrate of P-glycoprotein. Clin. Pharmacol. Ther.72,209219 (2002).
  • 102 Fromm MF, Kauffmann HM, Fritz P et al.: The effect of rifampin treatment on intestinal expression of human MRP transporters. Am. J. Pathol.157,15751580 (2000).
  • 103 Durr D, Stieger B, Kullak-Ublick GA et al.: St John’s Wort induces intestinal P-glycoprotein/MDR1 and intestinal and hepatic CYP3A4. Clin. Pharmacol. Ther.68, 598604 (2000).
  • 104 Richardson MA, Straus SE: Complementary and alternative medicine: opportunities and challenges for cancer management and research. Semin. Oncol.29,531545 (2002).
  • 105 Goto M, Masuda S, Saito H et al.: C3435T polymorphism in the MDR1 gene affects the enterocyte expression level of CYP3A4 rather than Pgp in recipients of living-donor liver transplantation. Pharmacogenetics12, 451457 (2002).
  • 106 Brinkmann U, Eichelbaum M: Polymorphisms in the ABC drug transporter gene MDR1. Pharmacogenomics J.1,5964 (2001).
  • 107 Brinkmann U, Roots I, Eichelbaum M: Pharmacogenetics of the human drug-transporter gene MDR1: impact of polymorphisms on pharmacotherapy. Drug Discov. Today6,835839 (2001).
  • 108 Ameyaw MM, Regateiro F, Li T et al.: MDR1 pharmacogenetics: frequency of the C3435T mutation in exon 26 is significantly influenced by ethnicity. Pharmacogenetics11,217221 (2001).
  • 109 Cascorbi I, Gerloff T, Johne A et al.: Frequency of single nucleotide polymorphisms in the P-glycoprotein drug transporter MDR1 gene in white subjects. Clin. Pharmacol. Ther.69,169174 (2001).• Describes significant ethnic variation in frequency of ABCB1 SNPs.
  • 110 Schaeffeler E, Eichelbaum M, Brinkmann U et al.: Frequency of C3435T polymorphism of MDR1 gene in African people. Lancet358,383384 (2001).
  • 111 Tang K, Ngoi SM, Gwee PC et al.: Distinct haplotype profiles and strong linkage disequilibrium at the MDR1 multidrug transporter gene locus in three ethnic Asian populations. Pharmacogenetics12,437450 (2002).
  • 112 Eap CB, Fellay J, Buclin T et al.: CYP3A activity measured by the midazolam test is not related to 3435 C > T polymorphism in the multiple drug resistance transporter gene. Pharmacogenetics14,255260 (2004).
  • 113 Taniguchi S, Mochida Y, Uchiumi T et al.: Genetic polymorphism at the 5′ regulatory region of multidrug resistance 1 (MDR1) and its association with interindividual variation of expression level in the colon. Mol. Cancer Ther.2,13511359 (2003).
  • 114 Johne A, Kopke K, Gerloff T et al.: Modulation of steady-state kinetics of digoxin by haplotypes of the P-glycoprotein MDR1 gene. Clin. Pharmacol. Ther.72, 584594 (2002).
  • 115 Chowbay B, Cumaraswamy S, Cheung YB, Zhou Q, Lee EJ: Genetic polymorphisms in MDR1 and CYP3A4 genes in Asians and the influence of MDR1 haplotypes on cyclosporin disposition in heart transplant recipients. Pharmacogenetics13,8995 (2003).
  • 116 Yi SY, Hong KS, Lim HS et al.: A variant 2677A allele of the MDR1 gene affects fexofenadine disposition. Clin. Pharmacol. Ther.76,418427 (2004).
  • 117 Skarke C, Jarrar M, Schmidt H et al.: Effects of ABCB1 (multidrug resistance transporter) gene mutations on disposition and central nervous effects of loperamide in healthy volunteers. Pharmacogenetics13, 651660 (2003).
  • 118 Sai K, Kaniwa N, Itoda M et al.: Haplotype analysis of ABCB1/MDR1 blocks in a Japanese population reveals genotype-dependent renal clearance of irinotecan. Pharmacogenetics13,741757 (2003).
  • 119 Goh BC, Lee SC, Wang LZ et al.: Explaining interindividual variability of docetaxel pharmacokinetics and pharmacodynamics in Asians through phenotyping and genotyping strategies. J. Clin. Oncol.20,36833690 (2002).
  • 120 Mathijssen RHJ, Marsh S, Karlsson MO et al.: Irinotecan pathway genotype analysis to predict pharmacokinetics. Clin. Cancer Res.9,32513258 (2003).
  • 121 Sparreboom A, Marsh S, Mathijssen RH, Verweij J, McLeod HL: Pharmacogenetics of tipifarnib (R115777) transport and metabolism in cancer patients. Invest. New Drugs22,285289 (2004).
  • 122 Bardelmeijer HA, Ouwehand M, Buckle T et al.: Low systemic exposure of oral docetaxel in mice resulting from extensive first-pass metabolism is boosted by ritonavir. Cancer Res.62,61586164 (2002).
  • 123 van Zuylen L, Verweij J, Nooter K, Brouwer E, Stoter G, Sparreboom A: Role of intestinal P-glycoprotein in the plasma and fecal disposition of docetaxel in humans. Clin. Cancer Res.6,25982603 (2000).
  • 124 Iyer L, Ramirez J, Shepard DR et al.: Biliary transport of irinotecan and metabolites in normal and P-glycoprotein-deficient mice. Cancer Chemother. Pharmacol.49,336341 (2002).
  • 125 Kehrer DF, Mathijssen RH, Verweij J, de Bruijn P, Sparreboom A: Modulation of irinotecan metabolism by ketoconazole. J. Clin. Oncol.20,31223129 (2002).
  • 126 Garner RC, Goris I, Laenen AA et al.: Evaluation of accelerator mass spectrometry in a human mass balance and pharmacokinetic study-experience with 14C-labeled (R)-6-[amino(4- chlorophenyl)(1-methyl-1H-imidazol-5-yl)methyl]-4-(3-chlorophenyl)-1- methyl-2(1H)-quinolinone (R115777), a farnesyl transferase inhibitor. Drug Metab. Dispos.30,823830 (2002).
  • 127 Jamroziak K, Robak T: Pharmacogenomics of MDR1/ABCB1 gene: the influence on risk and clinical outcome of haematological malignancies. Hematology9,91105 (2004).
  • 128 Illmer T, Schuler US, Thiede C et al.: MDR1 gene polymorphisms affect therapy outcome in acute myeloid leukemia patients. Cancer Res.62,49554962 (2002).
  • 129 Jamroziak K, Mlynarski W, Balcerczak E et al.: Functional C3435T polymorphism of MDR1 gene: an impact on genetic susceptibility and clinical outcome of childhood acute lymphoblastic leukemia. Eur. J. Haematol.72,314321 (2004).
  • 130 Kafka A, Sauer G, Jaeger C et al.: Polymorphism C3435T of the MDR-1 gene predicts response to preoperative chemotherapy in locally advanced breast cancer. Int. J. Oncol.22,11171121 (2003).
  • 131 Siegsmund M, Brinkmann U, Schaffeler E et al.: Association of the P-glycoprotein transporter MDR1(C3435T) polymorphism with the susceptibility to renal epithelial tumors. J. Am. Soc. Nephrol.13,18471854 (2002).
  • 132 Siddiqui A, Kerb R, Weale ME et al.: Association of multidrug resistance in epilepsy with a polymorphism in the drug-transporter gene ABCB1. N. Engl. J. Med.348,14421448 (2003).• Demonstration of a link between variants in ABCB1 and epilepsy.
  • 133 Schwab M, Schaeffeler E, Marx C et al.: Association between the C3435TMDR1 gene polymorphism and susceptibility for ulcerative colitis. Gastroenterology 124,2633 (2003).
  • 134 Brant SR, Panhuysen CI, Nicolae D et al.: MDR1 Ala893 polymorphism is associated with inflammatory bowel disease. Am. J. Hum. Genet.73,12821292 (2003).
  • 135 Glas J, Torok HP, Schiemann U, Folwaczny C: MDR1 gene polymorphism in ulcerative colitis. Gastroenterology126, 367 (2004).
  • 136 Potocnik U, Ferkolj I, Glavac D, Dean M: Polymorphisms in multidrug resistance 1 (MDR1) gene are associated with refractory Crohn disease and ulcerative colitis. Genes Immun.5,530539 (2004).
  • 137 Gazouli M, Zacharatos P, Gorgoulis V, Mantzaris G, Papalambros E, Ikonomopoulos J: The C3435TMDR1 gene polymorphism is not associated with susceptibility for ulcerative colitis in Greek population. Gastroenterology126,367369 (2004).
  • 138 Drozdzik M, Bialecka M, Mysliwiec K, Honczarenko K, Stankiewicz J, Sych Z: Polymorphism in the P-glycoprotein drug transporter MDR1 gene: a possible link between environmental and genetic factors in Parkinson’s disease. Pharmacogenetics13, 259263 (2003).
  • 139 Tan EK, Drozdzik M, Bialecka M et al.: Analysis of MDR1 haplotypes in Parkinson’s disease in a white population. Neurosci. Lett.372,240244 (2004).
  • 140 Asano T, Takahashi KA, Fujioka M et al.: ABCB1C3435T and G2677T/A polymorphism decreased the risk for steroid-induced osteonecrosis of the femoral head after kidney transplantation. Pharmacogenetics13,675682 (2003).
  • 141 Hebert MF, Dowling AL, Gierwatowski C et al.: Association between ABCB1 (multidrug resistance transporter) genotype and post-liver transplantation renal dysfunction in patients receiving calcineurin inhibitors. Pharmacogenetics13,661674 (2003).
  • 142 Fellay J, Marzolini C, Meaden ER et al.: Response to antiretroviral treatment in HIV-1-infected individuals with allelic variants of the multidrug resistance transporter 1: a pharmacogenetics study. Lancet359,3036 (2002).
  • 143 Brumme ZL, Dong WW, Chan KJ et al.: Influence of polymorphisms within the CX3CR1 and MDR-1 genes on initial antiretroviral therapy response. AIDS17, 201208 (2003).
  • 144 Haas DW, Wu H, Li H et al.: MDR1 gene polymorphisms and Phase I viral decay during HIV-1 infection: an adult AIDS Clinical Trials Group study. J. Acquir. Immune Defic. Syndr.34,295298 (2003).
  • 145 Bleiber G, May M, Suarez C et al.: MDR1 genetic polymorphism does not modify either cell permissiveness to HIV-1 or disease progression before treatment. J. Infect. Dis.189,583586 (2004).
  • 146 Nasi M, Borghi V, Pinti M et al.: MDR1 C3435T genetic polymorphism does not influence the response to antiretroviral therapy in drug-naive HIV-positive patients. AIDS17,16961698 (2003).
  • 147 Sparreboom A, Gelderblom H, Marsh S et al.: Diflomotecan pharmacokinetics in relation to ABCG2421C > A genotype. Clin. Pharmacol. Ther.76,3844 (2004).•• First demonstration of the impact of an ABCB2 SNP.
  • 148 Felici A, Verweij J, Sparreboom A: Dosing strategies for anticancer drugs: the good, the bad and body-surface area. Eur. J. Cancer38,16771684 (2002).
  • 149 Burger H, Van Tol H, Boersma AW et al.: Imatinib mesylate (STI571) is a substrate for the breast cancer resistance protein (BCRP)/ABCG2 drug pump. Blood104, 29402942 (2004).
  • 150 de Bruijn MH, Van de Bliek AM, Biedler JL, Borst P: Differential amplification and disproportionate expression of five genes in three multidrug-resistant Chinese hamster lung cell lines. Mol. Cell. Biol.6,47174722 (1986).
  • 151 Germann UA, Shlyakhter D, Mason VS et al.: Cellular and biochemical characterization of VX-710 as a chemosensitizer: reversal of P-glycoprotein-mediated multidrug resistance in vitro. Anti-Cancer Drugs8,125140 (1997).
  • 152 Kartner N, Shales M, Riordan JR, Ling V: Daunorubicin-resistant Chinese hamster ovary cells expressing resistance and a cell-surface P-glycoprotein. Cancer Res.43, 44134419 (1983).
  • 153 Che XF, Nakajima Y, Sumizawa T et al.: Reversal of P-glycoprotein mediated multidrug resistance by a newly synthesized 1, 4-benzothiazepine derivative, JTV-519. Cancer Lett.187,111119 (2002).
  • 154 Ringel I, Horwitz SB: Studies with RP 56976 (taxotere): a semisynthetic analogue of taxol. J. Natl Cancer Inst.83,288291 (1991).
  • 155 Sparreboom A, Planting AS, Jewell RC et al.: Clinical pharmacokinetics of doxorubicin in combination with GF120918, a potent inhibitor of MDR1 P-glycoprotein. Anti-Cancer Drugs10,719728 (1999).
  • 156 Ueda K, Cardarelli C, Gottesman MM, Pastan I: Expression of a full-length cDNA for the human ‘MDR1’ gene confers resistance to colchicine, doxorubicin, and vinblastine. Proc. Natl Acad. Sci. USA 84,30043008 (1987).
  • 157 van Zuylen L, Sparreboom A, van der Gaast A et al.: The orally administered P-glycoprotein inhibitor R101933 does not alter the plasma pharmacokinetics of docetaxel. Clin. Cancer Res.6,13651371 (2000).
  • 158 Pastan I, Gottesman MM, Ueda K, Lovelace E, Rutherford AV, Willingham MC: A retrovirus carrying an MDR1 cDNA confers multidrug resistance and polarized expression of P-glycoprotein in MDCK cells. Proc. Natl Acad. Sci. USA85,44864490 (1988).
  • 159 Boesch D, Gaveriaux C, Jachez B, Pourtier-Manzanedo A, Bollinger P, Loor F: In vivo circumvention of P-glycoprotein-mediated multidrug resistance of tumor cells with SDZ-PSC 833. Cancer Res. 51,42264233 (1991).
  • 160 Hegedus T, Orfi L, Seprodi A, Varadi A, Sarkadi B, Keri G: Interaction of tyrosine kinase inhibitors with the human multidrug transporter proteins, MDR1 and MRP1. Biochim. Biophys. Acta1578,318325 (2002).
  • 161 Dantzig AH, Shepard RL, Cao J et al.: Reversal of P-glycoprotein-mediated multidrug resistance by a potent cyclopropyldibenzosuberane modulator, LY335979. Cancer Res.56,41714179 (1996).
  • 162 Jansen WJ, Hulscher TM, van Ark-Otte J, Giaccone G, Pinedo HM, Boven E: CPT-11 sensitivity in relation to the expression of P170-glycoprotein and multidrug resistance-associated protein. Br. J. Cancer77,359365 (1998).
  • 163 Profit L, Eagling VA, Back DJ: Modulation of P-glycoprotein function in human lymphocytes and Caco-2 cell monolayers by HIV-1 protease inhibitors. AIDS 13,16231627 (1999).
  • 164 Schurr E, Raymond M, Bell JC, Gros P: Characterization of the multidrug resistance protein expressed in cell clones stably transfected with the mouse mdr1 cDNA. Cancer Res.49,27292733 (1989).
  • 165 Martin CM, Berridge G, Mistry P, Higgins C, Charlston P, Callaghan R: The molecular interaction of the high affinity reversal agent XR9576 with P-glycoprotein. Br. J. Pharmacol.128,403411 (1999).
  • 166 Lothstein L, Hsu SI, Horwitz SB, Greenberger LM: Alternate overexpression of two P-glycoprotein genes is associated with changes in multidrug resistance in a J774.2 cell line. J. Biol. Chem.264,1605416058 (1989).
  • 167 Van de Vrie W, Schellens JH, Loss WJ et al.: Modulation of multidrug resistance with dexniguldipine hydrochloride (B8509-035) in the CC531 rat colon carcinoma model. J. Cancer Res. Clin. Oncol.122,403408 (1996).
  • 168 Wolverton JS, Danks MK, Schmidt CA, Beck WT: Genetic characterization of the multidrug-resistant phenotype of VM-26-resistant human leukemic cells. Cancer Res.49,24222426 (1987).
  • 169 Hendricks CB, Rowinsky EK, Grochow LB, Donehower RC, Kaufmann SH: Effect of P-glycoprotein expression on the accumulation and cytotoxicity of topotecan (SK&F 104864), a new camptothecin analogue. Cancer Res.52,22682278 (1992).
  • 170 Horton JK, Houghton PJ, Houghton JA: Reciprocal cross-resistance in human rhabdomyosarcomas selected in vivo for primary resistance to vincristine and L-phenylalanine mustard. Cancer Res.47, 62886293 (1987).
  • 171 Schellens JH, Maliepaard M, Scheper RJ et al.: Transport of topoisomerase I inhibitors by the breast cancer resistance protein. Potential clinical implications. Ann. NY Acad. Sci.922,188194 (2000).
  • 172 Rajendra R, Gounder MK, Saleem A et al.: Differential effects of the breast cancer resistance protein on the cellular accumulation and cytotoxicity of 9-aminocamptothecin and 9-nitrocamptothecin. Cancer Res. 63,32283233 (2003).
  • 173 Erlichman C, Boerner SA, Hallgren CG et al.: The HER tyrosine kinase inhibitor CI1033 enhances cytotoxicity of 7-ethyl-10-hydroxycamptothecin and topotecan by inhibiting breast cancer resistance protein-mediated drug efflux. Cancer Res. 61,739748 (2001).
  • 174 Minderman H, O’Loughlin KL, Pendyala L, Baer MR: VX-710 (biricodar) increases drug retention and enhances chemosensitivity in resistant cells overexpressing P-glycoprotein, multidrug resistance protein, and breast cancer resistance protein. Clin. Cancer Res.10,18261834 (2004).
  • 175 Bates SE, Medina-Perez WY, Kohlhagen G et al.: ABCG2 mediates differential resistance to SN-38 and homocamptothecins. J. Pharmacol. Exp. Ther.310,836842 (2004).
  • 176 Sugimoto Y, Tsukahara S, Imai Y, Ueda K, Tsuruo T: Reversal of breast cancer resistance protein-mediated drug resistance by estrogen antagonists and agonists. Mol. Cancer Ther.2,105112 (2003).
  • 177 Ishii M, Iwahana M, Mitsui I et al.: Growth inhibitory effect of a new camptothecin analog, DX-8951f, on various drug-resistant sublines including BCRP-mediated camptothecin derivative-resistant variants derived from the human lung cancer cell line PC-6. Anti-Cancer Drugs11,353362 (2000).
  • 178 Burger H, Foekens JA, Look MP et al.: RNA expression of breast cancer resistance protein, lung resistance-related protein, multidrug resistance-associated proteins 1 and 2, and multidrug resistance gene 1 in breast cancer: correlation with chemotherapeutic response. Clin. Cancer Res.9,827836 (2003).
  • 179 Chen ZS, Robey RW, Belinsky MG et al.: Transport of methotrexate, methotrexate polyglutamates, and 17β-estradiol 17-(β-D-glucuronide) by ABCG2: effects of acquired mutations at R482 on methotrexate transport. Cancer Res.63,40484054 (2003).
  • 180 Yang CH, Chen YC, Kuo ML: Novobiocin sensitizes BCRP/MXR/ABCP overexpressing topotecan-resistant human breast carcinoma cells to topotecan and mitoxantrone. Anti-Cancer Res. 23,25192523 (2003).
  • 181 Robey RW, Medina-Perez WY, Nishiyama K et al.: Overexpression of the ATP-binding cassette half-transporter, ABCG2 (Mxr/BCrp/ABCP1), in flavopiridol-resistant human breast cancer cells. Clin. Cancer Res.7,145152 (2001).
  • 182 Jones HE, Brenwald NP, Owen KA, Gill MJ: A multidrug efflux phenotype mutant of Streptococcus pyogenes. J. Antimicrob. Chemother.51,707710 (2003).
  • 183 Houghton PJ, Germain GS, Harwood FC et al.: Imatinib mesylate is a potent inhibitor of the ABCG2 (BCRP) transporter and reverses resistance to topotecan and SN-38 in vitro. Cancer Res.64,23332337 (2004).
  • 184 Komatani H, Kotani H, Hara Y et al.: Identification of breast cancer resistant protein/mitoxantrone resistance/placenta-specific, ATP-binding cassette transporter as a transporter of NB-506 and J-107088, topoisomerase I inhibitors with an indolocarbazole structure. Cancer Res.61, 28272832 (2001).
  • 185 Gupta A, Zhang Y, Unadkat JD, Mao Q: HIV protease inhibitors are inhibitors but not substrates of the human breast cancer resistance protein (BCRP/ABCG2). J. Pharmacol. Exp. Ther.310, 334–341 (2004).
  • 186 Minderman H, Brooks TA, O’Loughlin KL, Ojima I, Bernacki RJ, Baer MR: Broad-spectrum modulation of ATP-binding cassette transport proteins by the taxane derivatives ortataxel (IDN-5109, BAY 59-8862) and tRA96023. Cancer Chemother. Pharmacol.53,363369 (2004).
  • 187 Woehlecke H, Pohl A, Alder-Baerens N, Lage H, Herrmann A: Enhanced exposure of phosphatidylserine in human gastric carcinoma cells overexpressing the half-size ABC transporter BCRP (ABCG2). Biochem. J.376,489495 (2003).
  • 188 Kawabata S, Oka M, Shiozawa K et al.: Breast cancer resistance protein directly confers SN-38 resistance of lung cancer cells. Biochem. Biophys. Res. Commun.280, 1216 1223 (2001).
  • 189 Maliepaard M, van Gastelen MA, de Jong LA et al.: Overexpression of the BCRP/MXR/ABCP gene in a topotecan-selected ovarian tumor cell line. Cancer Res.59,45594563 (1999).
  • 190 van der Heijden J, de Jong MC, Dijkmans BA et al.: Acquired resistance of human T cells to sulfasalazine: stability of the resistant phenotype and sensitivity to non-related DMARDs. Ann. Rheum. Dis.63,131137 (2004).
  • 191 Drescher S, van der Kuip H, Schaffeler E et al.: MDR1 gene-related clonal selection and P-glycoprotein function and expression in relapsed or refractory acute myeloid leukemia. Pharmacogenetics11,293298 (2001).
  • 192 Diah SK, Smitherman PK, Aldridge J et al.: Resistance to mitoxantrone in multidrug-resistant MCF7 breast cancer cells: evaluation of mitoxantrone transport and the role of multidrug resistance protein family proteins. Cancer Res.61,54615467 (2001).
  • 193 Oselin K, Gerloff T, Mrozikiewicz PM, Pahkla R, Roots I: MDR1 polymorphisms G2677T in exon 21 and C3435T in exon 26 fail to affect rhodamine 123 efflux in peripheral blood lymphocytes. Fundam. Clin. Pharmacol.17,463469 (2003).
  • 194 Oselin K, Nowakowski-Gashaw I, Mrozikiewicz PM, Wolbergs D, Pahkla R, Roots I: Quantitative determination of MDR1 mRNA expression in peripheral blood lymphocytes: a possible role of genetic polymorphisms in the MDR1 gene. Eur. J. Clin. Invest.33,261267 (2003).
  • 195 Siegmund W, Ludwig K, Giessmann T et al.: The effects of the human MDR1 genotype on the expression of duodenal P-glycoprotein and disposition of the probe drug talinolol. Clin. Pharmacol. Ther.72, 572583 (2002).
  • 196 Nakamura T, Sakaeda T, Horinouchi M et al.: Effect of the mutation (C3435T) at exon 26 of the MDR1 gene on expression level of MDR1 messenger ribonucleic acid in duodenal enterocytes of healthy Japanese subjects. Clin. Pharmacol. Ther. 71,297303 (2002).
  • 197 Nakamura T: [MDR1 genotypes related to pharmacokinetics and MDR1 expression]. Yakugaku Zasshi.123,773779 (2003).
  • 198 Moriya Y, Nakamura T, Horinouchi M et al.: Effects of polymorphisms of MDR1, MRP1, and MRP2 genes on their mRNAS expression levels in duodenal enterocytes of healthy Japanese subjects. Biol. Pharm. Bull.25,13561359 (2002).
  • 199 Meissner K, Jedlitschky G, Meyer zu Schwabedissen H et al.: Modulation of multidrug resistance P-glycoprotein 1 (ABCB1) expression in human heart by hereditary polymorphisms. Pharmacogenetics14,381385 (2004).
  • 200 Tanabe M, Ieiri I, Nagata N et al.: Expression of P-glycoprotein in human placenta: relation to genetic polymorphism of the multidrug resistance (MDR)-1 gene. J. Pharmacol. Exp. Ther.297,11371143 (2001).
  • 201 Hitzl M, Schaeffeler E, Hocher B et al.: Variable expression of P-glycoprotein in the human placenta and its association with mutations of the multidrug resistance 1 gene (MDR1, ABCB1). Pharmacogenetics14, 309318 (2004).
  • 202 Uwai Y, Masuda S, Goto M et al.: Common single nucleotide polymorphisms of the MDR1 gene have no influence on its mRNA expression level of normal kidney cortex and renal cell carcinoma in Japanese nephrectomized patients. J. Hum. Genet.49, 4045 (2004).
  • 203 Puisset F, Chatelut E, Dalenc F et al.: Dexamethasone as a probe for docetaxel clearance. Cancer Chemother. Pharmacol.54, 265272 (2004).
  • 204 Isla D, Sarries C, Rosell R et al.: Single nucleotide polymorphisms and outcome in docetaxel-cisplatin-treated advanced non-small-cell lung cancer. Ann. Oncol.15, 11941203 (2004).
  • 205 Kishi S, Yang W, Boureau B et al.: Effects of prednisone and genetic polymorphisms on etoposide disposition in children with acute lymphoblastic leukemia. Blood103,6772 (2004).
  • 206 Mathijssen RH, de Jong FA, van Schaik RH et al.: Prediction of irinotecan pharmacokinetics by use of cytochrome P450 3A4 phenotyping probes. J. Natl Cancer Inst.96,15851592 (2004).
  • 207 Plasschaert SL, Groninger E, Boezen M et al.: Influence of functional polymorphisms of the MDR1 gene on vincristine pharmacokinetics in childhood acute lymphoblastic leukemia. Clin. Pharmacol. Ther.76,220229 (2004).
  • 208 Becquemont L, Verstuyft C, Kerb R et al.: Effect of grapefruit juice on digoxin pharmacokinetics in humans. Clin. Pharmacol. Ther.70,311316 (2001).
  • 209 Sakaeda T, Nakamura T, Horinouchi M et al.: MDR1 genotype-related pharmacokinetics of digoxin after single oral administration in healthy Japanese subjects. Pharm. Res.18,14001404 (2001).
  • 210 Gerloff T, Schaefer M, Johne A et al.: MDR1 genotypes do not influence the absorption of a single oral dose of 1 mg digoxin in healthy white males. Br. J. Clin. Pharmacol.54,610616 (2002).
  • 211 Horinouchi M, Sakaeda T, Nakamura E et al.: Significant genetic linkage of MDR1 polymorphisms at positions 3435 and 2677: functional relevance to pharmacokinetics of digoxin. Pharm. Res.19,15811585 (2002).
  • 212 Verstuyft C, Schwab M, Schaeffeler E et al.: Digoxin pharmacokinetics and MDR1 genetic polymorphisms. Eur. J. Clin. Pharmacol.58,809812 (2003).
  • 213 Parker RB, Yates CR, Soberman JE, Laizure SC: Effects of grapefruit juice on intestinal P-glycoprotein: evaluation using digoxin in humans. Pharmacotherapy23, 979987 (2003).
  • 214 Morita Y, Sakaeda T, Horinouchi M et al.: MDR1 genotype-related duodenal absorption rate of digoxin in healthy Japanese subjects. Pharm. Res.20,552556 (2003).
  • 215 von Ahsen N, Richter M, Grupp C, Ringe B, Oellerich M, Armstrong VW: No influence of the MDR-1 C3435T polymorphism or a CYP3A4 promoter polymorphism (CYP3A4-V allele) on dose-adjusted cyclosporin A trough concentrations or rejection incidence in stable renal transplant recipients. Clin. Chem.47,10481052 (2001).
  • 216 Min DI, Ellingrod VL: C3435T mutation in exon 26 of the human MDR1 gene and cyclosporine pharmacokinetics in healthy subjects. Ther. Drug Monit.24,400404 (2002).
  • 217 Hesselink DA, van Schaik RH, van der Heiden IP et al.: Genetic polymorphisms of the CYP3A4, CYP3A5, and MDR-1 genes and pharmacokinetics of the calcineurin inhibitors cyclosporine and tacrolimus. Clin. Pharmacol. Ther. 74,245254 (2003).
  • 218 Mai I, Stormer E, Goldammer M et al.: MDR1 haplotypes do not affect the steady-state pharmacokinetics of cyclosporine in renal transplant patients. J. Clin. Pharmacol.43,11011107 (2003).
  • 219 Yates CR, Zhang W, Song P et al.: The effect of CYP3A5 and MDR1 polymorphic expression on cyclosporine oral disposition in renal transplant patients. J. Clin. Pharmacol.43,555564 (2003).
  • 220 Haufroid V, Mourad M, Van Kerckhove V et al.: The effect of CYP3A5 and MDR1 (ABCB1) polymorphisms on cyclosporine and tacrolimus dose requirements and through blood levels in stable renal transplant patients. Pharmacogenetics14,147154 (2004).
  • 221 Anglicheau D, Thervet E, Etienne I et al.: CYP3A5 and MDR1 genetic polymorphisms and cyclosporine pharmacokinetics after renal transplantation. Clin. Pharmacol. Ther.75, 422433 (2004).
  • 222 Bonhomme-Faivre L, Devocelle A, Saliba F et al.: MDR-1 C3435T polymorphism influences cyclosporine a dose requirement in liver-transplant recipients. Transplantation78,2125 (2004).
  • 223 Hesselink DA, van Gelder T, van Schaik RH et al.: Population pharmacokinetics of cyclosporine in kidney and heart transplant recipients and the influence of ethnicity and genetic polymorphisms in the MDR-1, CYP3A4, and CYP3A5 genes. Clin. Pharmacol. Ther.76,545556 (2004).
  • 224 Macphee IA, Fredericks S, Tai T et al.: Tacrolimus pharmacogenetics: polymorphisms associated with expression of cytochrome P4503A5 and P-glycoprotein correlate with dose requirement. Transplantation74,14861489 (2002).
  • 225 Yamauchi A, Ieiri I, Kataoka Y et al.: Neurotoxicity induced by tacrolimus after liver transplantation: relation to genetic polymorphisms of the ABCB1 (MDR1) gene. Transplantation74,571572 (2002).
  • 226 Zheng H, Webber S, Zeevi A et al.: Tacrolimus dosing in pediatric heart transplant patients is related to CYP3A5 and MDR1 polymorphisms. Am. J. Transplant.3,477483 (2003).
  • 227 Anglicheau D, Verstuyft C, Laurent-Puig P et al.: Association of the multidrug resistance-1 gene single-nucleotide polymorphisms with the tacrolimus dose requirements in renal transplant recipients. J. Am. Soc. Nephrol.14,18891896 (2003).
  • 228 Zheng H, Zeevi A, Schuetz E et al.: Tacrolimus dosing in adult lung transplant patients is related to cytochrome P4503A5 gene polymorphism. J. Clin. Pharmacol.44, 135140 (2004).
  • 229 Mai I, Perloff ES, Bauer S et al.: MDR1 haplotypes derived from exons 21 and 26 do not affect the steady-state pharmacokinetics of tacrolimus in renal transplant patients. Br. J. Clin. Pharmacol.58,548553 (2004).
  • 230 Tsuchiya N, Satoh S, Tada H et al.: Influence of CYP3A5 and MDR1 (ABCB1) polymorphisms on the pharmacokinetics of tacrolimus in renal transplant recipients. Transplantation78,11821187 (2004).
  • 231 Putnam W, Desai DG, Huang YJ, Woo JM, Benet LZ: The effect of induction conditions and MDR1 genotypes on dicloxacillin pharmacokinetics. Clin. Pharmacol. Ther.73, 57 (2003).
  • 232 Haas DW, Ribaudo HJ, Kim RB et al.: Pharmacogenetics of efavirenz and central nervous system side effects: an Adult AIDS Clinical Trials Group study. AIDS18, 23912400 (2004).
  • 233 Drescher S, Schaeffeler E, Hitzl M et al.: MDR1 gene polymorphisms and disposition of the P-glycoprotein substrate fexofenadine. Br. J. Clin. Pharmacol. 53,526534 (2002).
  • 234 Pauli-Magnus C, Feiner J, Brett C, Lin E, Kroetz DL: No effect of MDR1 C3435T variant on loperamide disposition and central nervous system effects. Clin. Pharmacol. Ther.74,487498 (2003).• Describes the usefulness of using ABCB1 haplotypes.
  • 235 Roberts RL, Joyce PR, Mulder RT, Begg EJ, Kennedy MA: A common P-glycoprotein polymorphism is associated with nortriptyline-induced postural hypotension in patients treated for major depression. Pharmacogenomics J.2,191196 (2002).
  • 236 Kerb R, Aynacioglu AS, Brockmoller J et al.: The predictive value of MDR1, CYP2C9, and CYP2C19 polymorphisms for phenytoin plasma levels. Pharmacogenomics J.1,204210 (2001).
  • 237 Zheng H, Webber S, Zeevi A et al.: The MDR1 polymorphisms at exon 21 and 26 predict steroid weaning in pediatric heart transplant patients. Hum. Immunol.63,765770 (2002).
  • 238 Wadelius M, Sorlin K, Wallerman O et al.: Warfarin sensitivity related to CYP2C9, CYP3A5, ABCB1 (MDR1) and other factors. Pharmacogenomics J.4,4048 (2004).

Website

  • 301 www.gene.ucl.ac.uk/nomenclature/genefamily/ abc.html Human ABC transporter genes (accessed February 2005).