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Cancer Chemotherapy and Pharmacology
Published in: Cancer Chemotherapy and Pharmacology 3/2016

01-09-2016 | Review Article

Pharmacokinetic variations in cancer patients with liver dysfunction: applications and challenges of pharmacometabolomics

Authors: Ali Aboel Dahab, Dhia El-Hag, Gamal M. Moutamed, Sarah Aboel Dahab, Ramadan Abuknesha, Norman W. Smith

Published in: Cancer Chemotherapy and Pharmacology | Issue 3/2016

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Abstract

Purpose

In cancer patients, pharmacokinetic variations between individuals and within individuals due to impairments in organs’ function and other reasons such as genetic polymorphisms represent a major problem in disease management, which can result in unpredictable toxicity and variable antineoplastic effects. Addressing pharmacokinetic variations in cancer patients with liver dysfunction and their implications on anticancer and analgesic drugs, in addition to the use of advanced analytical techniques such as metabolomics and pharmacometabolomics, to monitor altered kinetic and discover metabolic biomarkers during therapeutic intervention will help in understanding and reducing pharmacokinetic variations of drugs in cancer patients as a step forward towards personalised medicine.

Methods

Reviewing published literature addressing and/or related to complications resulting from altered pharmacokinetics (PKs) in cancer patients with liver dysfunction, anticancer and analgesic drugs, evaluating recent advances of pharmacokinetic detection using metabolomics/pharmacometabolomics and the challenges that are currently facing these techniques.

Results

The current situation presents a pressing need to reduce pharmacokinetic variations of drugs in cancer patients. Although most of the omics technologies are not entirely focussed on the study of pharmacokinetic variations and some studies are met with uncertainty, the use of pharmacometabolomics combined with other omics technology such as pharmacogenomics can provide clues to personalised cancer treatments by providing useful information about the cancer patient’s response to medical interventions via identification of patients’ dependent variables, understanding of correlations between individuals and population PKs, and therapy outcomes to achieve optimum therapeutic effects with minimum toxicity. We also propose an approach for PKs' evaluation using pharmacometabolomics.
Literature
1.
Roberts JA (2011) Using PK/PD to optimize antibiotic dosing for critically ill patients. Curr Pharm Biotechnol 12:2070–2079PubMedCrossRef
2.
Palmer AM (2003) New horizons in drug metabolism, pharmacokinetics and drug discovery. Drug News Perspect 16:57–62PubMed
3.
Danielson PB (2002) The cytochrome P450 superfamily: biochemistry, evolution and drug metabolism in humans. Curr Drug Metab 3:561–597PubMedCrossRef
4.
Saito C, Yan HM, Artigues A, Villar MT, Farhood A, Jaeschke H (2010) Mechanism of protection by metallothionein against acetaminophen hepatotoxicity. Toxicol Appl Pharmacol 242:182–190CrossRefPubMed
5.
Le Couteur DG, Fraser R, Hilmer S, Rivory LP, McLean AJ (2005) The hepatic sinusoid in aging and cirrhosis: effects on hepatic substrate disposition and drug clearance. Clin Pharmacokinet 44:187–200PubMedCrossRef
6.
Hanje AJ, Patel T (2007) Preoperative evaluation of patients with liver disease. Nat Clin Pract Gastroenterol Hepatol 4:266–276PubMedCrossRef
7.
Lin XB, Farhangfar A, Valcheva R, Sawyer MB, Dieleman L, Schieber A et al (2014) The role of intestinal microbiota in development of irinotecan toxicity and in toxicity reduction through dietary fibres in rats. PLoS One 9:e83644PubMedPubMedCentralCrossRef
8.
Dubey A, Rangarajan A, Pal D, Atreya HS (2015) Pattern recognition-based approach for identifying metabolites in nuclear magnetic resonance-based metabolomics. Anal Chem 87:7148–7155PubMedCrossRef
9.
Kaddurah-Daouk R, Weinshilboum RM (2014) Pharmacometabolomics: implications for clinical pharmacology and systems pharmacology. Clin Pharmacol Ther 95:154–167PubMedCrossRef
10.
Kimbung S, Loman N, Hedenfalk I (2015) Clinical and molecular complexity of breast cancer metastases. Semin Cancer Biol 35:85–95CrossRefPubMed
11.
Brucher BL, Jamall IS (2014) Cell-cell communication in the tumor microenvironment, carcinogenesis, and anticancer treatment. Cell Physiol Biochem 34:213–243PubMedCrossRef
12.
Williams ML, Bhargava P, Cherrouk I, Marshall JL, Flockhart DA, Wainer IW (2000) A discordance of the cytochrome P450 2C19 genotype and phenotype in patients with advanced cancer. Br J Clin Pharmacol 49:485–488PubMedPubMedCentralCrossRef
13.
Baker SD, van Schaik RH, Rivory LP, Ten Tije AJ, Dinh K, Graveland WJ et al (2004) Factors affecting cytochrome P-450 3A activity in cancer patients. Clin Cancer Res 10:8341–8350PubMedCrossRef
14.
Slaviero KA, Clarke SJ, Rivory LP (2003) Inflammatory response: an unrecognised source of variability in the pharmacokinetics and pharmacodynamics of cancer chemotherapy. Lancet Oncol 4:224–232PubMedCrossRef
15.
Frye RF, Zgheib NK, Matzke GR, Chaves-Gnecco D, Rabinovitz M, Shaikh OS et al (2006) Liver disease selectively modulates cytochrome P450-mediated metabolism. Clin Pharmacol Ther 80:235–245PubMedCrossRef
16.
Chen M, Suzuki A, Borlak J, Andrade RJ, Lucena MI (2015) Drug-induced liver injury: interactions between drug properties and host factors. J Hepatol 63:503–514PubMedCrossRef
17.
Syn NL, Wang L, Wong AL, Soe MY, Chuah B, Chan D et al (2016) Dose modifications in Asian cancer patients with hepatic dysfunction receiving weekly docetaxel: a prospective pharmacokinetic and safety study. Cancer Sci 107:173–180PubMedPubMedCentralCrossRef
18.
LoRusso PM, Venkatakrishnan K, Ramanathan RK, Sarantopoulos J, Mulkerin D, Shibata SI et al (2012) Pharmacokinetics and safety of bortezomib in patients with advanced malignancies and varying degrees of liver dysfunction: phase I NCI Organ Dysfunction Working Group Study NCI-6432. Clin Cancer Res 18:2954–2963CrossRefPubMed
19.
Shibata SI, Chung V, Synold TW, Longmate JA, Suttle AB, Ottesen LH et al (2013) Phase I study of pazopanib in patients with advanced solid tumors and hepatic dysfunction: a National Cancer Institute Organ Dysfunction Working Group study. Clin Cancer Res 19:3631–3639PubMedPubMedCentralCrossRef
20.
Ennulat D, Magid-Slav M, Rehm S, Tatsuoka KS (2010) Diagnostic performance of traditional hepatobiliary biomarkers of drug-induced liver injury in the rat. Toxicol Sci 116:397–412PubMedCrossRef
21.
Aboel Dahab A, Smith NW (2012) Drug-induced hepatotoxicity: application of mass spectrometry based metabonomics. Anal Methods 4:1887–1902CrossRef
22.
Nikiforov A, Kulikova V, Ziegler M (2015) The human NAD metabolome: functions, metabolism and compartmentalization. Crit Rev Biochem Mol Biol 50:284–297PubMedPubMedCentralCrossRef
23.
Murray KF, Carithers RL Jr (2005) AASLD practice guidelines: evaluation of the patient for liver transplantation. Hepatology 41:1407–1432PubMedCrossRef
24.
Blot SI, Pea F, Lipman J (2014) The effect of pathophysiology on pharmacokinetics in the critically ill patient—concepts appraised by the example of antimicrobial agents. Adv Drug Deliv Rev 77:3–11PubMedCrossRef
25.
Sandri AM, Landersdorfer CB, Jacob J, Boniatti MM, Dalarosa MG, Falci DR et al (2013) Population pharmacokinetics of intravenous polymyxin B in critically ill patients: implications for selection of dosage regimens. Clin Infect Dis 57:524–531PubMedCrossRef
26.
Vaja R, McNicol L, Sisley I (2009) Anaesthesia for patients with liver disease. CEACCP 10:15–19
27.
Diakos CI, Charles KA, McMillan DC, Clarke SJ (2014) Cancer-related inflammation and treatment effectiveness. Lancet Oncol 15:e493–e503PubMedCrossRef
28.
Hebert MF (1998) Guide to drug dosage in hepatic disease. In: Holford N (ed) Drug data handbook, 3rd edn. Adis International, Auckland, pp 121–179
29.
Tchambaz L, Schlatter C, Jakob M, Krahenbuhl A, Wolf P, Krahenbuhl S (2006) Dose adaptation of antineoplastic drugs in patients with liver disease. Drug Saf 29:509–522PubMedCrossRef
30.
Gao B, Yeap S, Clements A, Balakrishnar B, Wong M, Gurney H (2012) Evidence for therapeutic drug monitoring of targeted anticancer therapies. Journal of clinical oncology: official journal of the American Society of Clinical Oncology 30:4017–4025CrossRef
31.
Eklund JW, Trifilio S, Mulcahy MF (2005) Chemotherapy dosing in the setting of liver dysfunction. Oncology (Williston Park) 19:1057–1063 (discussion 1063–1054, 1069)
32.
Yang J, Shord S, Zhao H, Men Y, Rahman A (2013) Are hepatic impairment studies necessary for therapeutic proteins? Clin Ther 35:1444–1451PubMedCrossRef
33.
Kitzen JJ, Puozzo C, de Jonge MJ, Brandely M, Verweij J (2010) Mild to moderate liver dysfunction does not require dose reduction of oral or intravenous vinorelbine: results of a pharmacokinetic study. Eur J Cancer 46:266–269PubMedCrossRef
34.
Innocenti F, Schilsky RL, Ramirez J, Janisch L, Undevia S, House LK et al (2014) Dose-finding and pharmacokinetic study to optimize the dosing of irinotecan according to the UGT1A1 genotype of patients with cancer. J Clin Oncol 32:2328–2334PubMedPubMedCentralCrossRef
35.
Berezhkovskiy LM (2011) The corrected traditional equations for calculation of hepatic clearance that account for the difference in drug ionization in extracellular and intracellular tissue water and the corresponding corrected PBPK equation. J Pharm Sci 100:1167–1183PubMedCrossRef
36.
Kotb HI, Fouad IA, Fares KM, Mostafa MG, Abd El-Rahman AM (2008) Pharmacokinetics of oral tramadol in patients with liver cancer. Journal of opioid management 4:99–104PubMed
37.
Nguyen HM, Cutie AJ, Pham DQ (2010) How to manage medications in the setting of liver disease with the application of six questions. Int J Clin Pract 64:858–867CrossRefPubMed
38.
Tod M, Mir O, Bancelin N, Coriat R, Thomas-Schoemann A, Taieb F et al (2011) Functional and clinical evidence of the influence of sorafenib binding to albumin on sorafenib disposition in adult cancer patients. Pharm Res 28:3199–3207PubMedCrossRef
39.
Verbeeck RK (2008) Pharmacokinetics and dosage adjustment in patients with hepatic dysfunction. Eur J Clin Pharmacol 64:1147–1161PubMedCrossRef
40.
Petrovic V, Teng S, Piquette-Miller M (2007) Regulation of drug transporters during infection and inflammation. Mol Interventions 7:99–111CrossRef
41.
el Touny M, el Guinaidy M, Abdel Barry M, Osman L, Sabbour MS (1992) Pharmacokinetics of aztreonam in patients with liver cirrhosis and ascites. The Journal of antimicrobial chemotherapy 30:387–395PubMedCrossRef
42.
el Touny M, el Guinaidy M, Abdel Bary M, Osman L, Sabbour MS (1992) Pharmacokinetics of cefodizime in patients with liver cirrhosis and ascites. Chemotherapy 38:201–205PubMedCrossRef
43.
Schmitt-Hoffmann A, Roos B, Spickermann J, Heep M, Peterfai E, Edwards DJ et al (2009) Effect of mild and moderate liver disease on the pharmacokinetics of isavuconazole after intravenous and oral administration of a single dose of the prodrug BAL8557. Antimicrob Agents Chemother 53:4885–4890PubMedPubMedCentralCrossRef
44.
Mano MS, Cassidy J, Canney P (2005) Liver metastases from breast cancer: management of patients with significant liver dysfunction. Cancer Treat Rev 31:35–48PubMedCrossRef
45.
Rodés J, Benhamou J-P, Blei A, Reichen J, Rizzetto M (2007) Textbook of hepatology: from basic science to clinical practice. Wiley, MaldenCrossRef
46.
Turner R, Lozoya O, Wang Y, Cardinale V, Gaudio E, Alpini G et al (2011) Human hepatic stem cell and maturational liver lineage biology. Hepatology 53:1035–1045PubMedPubMedCentralCrossRef
47.
48.
49.
van Erp NP, Gelderblom H, Guchelaar HJ (2009) Clinical pharmacokinetics of tyrosine kinase inhibitors. Cancer Treat Rev 35:692–706PubMedCrossRef
50.
Li J, Karlsson MO, Brahmer J, Spitz A, Zhao M, Hidalgo M et al (2006) CYP3A phenotyping approach to predict systemic exposure to EGFR tyrosine kinase inhibitors. J Natl Cancer Inst 98:1714–1723PubMedCrossRef
51.
Holohan C, Van Schaeybroeck S, Longley DB, Johnston PG (2013) Cancer drug resistance: an evolving paradigm. Nat Rev Cancer 13:714–726CrossRefPubMed
52.
Meza-Junco J, Chu QS, Christensen O, Rajagopalan P, Das S, Stefanyschyn R et al (2009) UGT1A1 polymorphism and hyperbilirubinemia in a patient who received sorafenib. Cancer Chemother Pharmacol 65:1–4PubMedCrossRef
53.
Johnson PJ, Berhane S, Kagebayashi C, Satomura S, Teng M, Reeves HL et al (2015) Assessment of liver function in patients with hepatocellular carcinoma: a new evidence-based approach—the ALBI grade. J Clin Oncol 33:550–558PubMedCrossRef
54.
55.
Chandra P, Brouwer KL (2004) The complexities of hepatic drug transport: current knowledge and emerging concepts. Pharm Res 21:719–735PubMedCrossRef
56.
Iida A, Saito S, Sekine A, Mishima C, Kitamura Y, Kondo K et al (2002) 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 47:285–310PubMedCrossRef
57.
58.
Sakurai A, Kurata A, Onishi Y, Hirano H, Ishikawa T (2007) Prediction of drug-induced intrahepatic cholestasis: in vitro screening and QSAR analysis of drugs inhibiting the human bile salt export pump. Expert Opin Drug Saf 6:71–86PubMedCrossRef
59.
60.
Woodhead JL, Yang K, Siler SQ, Watkins PB, Brouwer KL, Barton HA et al (2014) Exploring BSEP inhibition-mediated toxicity with a mechanistic model of drug-induced liver injury. Front Pharmacol 5:240PubMedCrossRefPubMedCentral
61.
62.
Vogiatzi P, Claudio PP (2010) Efficacy of abiraterone acetate in post-docetaxel castration-resistant prostate cancer. Expert Rev Anticancer Ther 10:1027–1030PubMedCrossRef
63.
Ghoshal K, Bai S (2007) DNA methyltransferases as targets for cancer therapy. Drugs Today (Barc) 43:395–422CrossRef
64.
Gerber HP, Ferrara N (2005) Pharmacology and pharmacodynamics of bevacizumab as monotherapy or in combination with cytotoxic therapy in preclinical studies. Cancer Res 65:671–680PubMed
65.
Borgan E, Lindholm EM, Moestue S, Maelandsmo GM, Lingjaerde OC, Gribbestad IS et al (2013) Subtype-specific response to bevacizumab is reflected in the metabolome and transcriptome of breast cancer xenografts. Mol Oncol 7:130–142PubMedCrossRef
66.
Tsai DE, Luger SM, Andreadis C, Vogl DT, Kemner A, Potuzak M et al (2008) A phase I study of bexarotene, a retinoic X receptor agonist, in non-M3 acute myeloid leukemia. Clin Cancer Res 14:5619–5625PubMedCrossRef
67.
Valdez BC, Andersson BS (2010) Interstrand crosslink inducing agents in pretransplant conditioning therapy for hematologic malignancies. Environ Mol Mutagen 51:659–668PubMedPubMedCentral
68.
Marchi E, Paoluzzi L, Scotto L, Seshan VE, Zain JM, Zinzani PL et al (2010) Pralatrexate is synergistic with the proteasome inhibitor bortezomib in in vitro and in vivo models of T-cell lymphoid malignancies. Clin Cancer Res 16:3648–3658PubMedCrossRef
69.
Hsieh FY, Tengstrand E, Pekol TM, Guerciolini R, Miwa G (2009) Elucidation of potential bortezomib response markers in mutliple myeloma patients. J Pharm Biomed Anal 49:115–122PubMedCrossRef
70.
Koukourakis GV, Kouloulias V, Koukourakis MJ, Zacharias GA, Zabatis H, Kouvaris J (2008) Efficacy of the oral fluorouracil pro-drug capecitabine in cancer treatment: a review. Molecules 13:1897–1922PubMedCrossRef
71.
Chung YL, Troy H, Judson IR, Leek R, Leach MO, Stubbs M et al (2004) Noninvasive measurements of capecitabine metabolism in bladder tumors overexpressing thymidine phosphorylase by fluorine-19 magnetic resonance spectroscopy. Clin Cancer Res 10:3863–3870PubMedCrossRef
72.
Doroshenko N, Doroshenko P (2004) The glutathione reductase inhibitor carmustine induces an influx of Ca2+ in PC12 cells. Eur J Pharmacol 497:17–24PubMedCrossRef
73.
Parker LJ, Ciccone S, Italiano LC, Primavera A, Oakley AJ, Morton CJ et al (2008) The anti-cancer drug chlorambucil as a substrate for the human polymorphic enzyme glutathione transferase P1-1: kinetic properties and crystallographic characterisation of allelic variants. J Mol Biol 380:131–144PubMedCrossRef
74.
75.
Garcia Sar D, Montes-Bayon M, Aguado Ortiz L, Blanco-Gonzalez E, Sierra LM, Sanz-Medel A (2008) In vivo detection of DNA adducts induced by cisplatin using capillary HPLC-ICP-MS and their correlation with genotoxic damage in Drosophila melanogaster. Anal Bioanal Chem 390:37–44PubMedCrossRef
76.
Kwon HN, Kim M, Wen H, Kang S, Yang HJ, Choi MJ et al (2011) Predicting idiopathic toxicity of cisplatin by a pharmacometabonomic approach. Kidney Int 79:529–537PubMedCrossRef
77.
Magi-Galluzzi C, Zhou M, Reuther AM, Dreicer R, Klein EA (2007) Neoadjuvant docetaxel treatment for locally advanced prostate cancer: a clinicopathologic study. Cancer 110:1248–1254PubMedCrossRef
78.
Bayet-Robert M, Morvan D, Chollet P, Barthomeuf C (2010) Pharmacometabolomics of docetaxel-treated human MCF7 breast cancer cells provides evidence of varying cellular responses at high and low doses. Breast Cancer Res Treat 120:613–626PubMedCrossRef
79.
Koehn H, Magan N, Isaacs RJ, Stowell KM (2007) Differential regulation of DNA repair protein Rad51 in human tumour cell lines exposed to doxorubicin. Anticancer Drugs 18:419–425PubMedCrossRef
80.
Cao B, Li M, Zha W, Zhao Q, Gu R, Liu L et al (2013) Metabolomic approach to evaluating adriamycin pharmacodynamics and resistance in breast cancer cells. Metabolomics 9:960–973PubMedPubMedCentralCrossRef
81.
Liang CH, Shiu LY, Chang LC, Sheu HM, Kuo KW (2007) Solamargine upregulation of Fas, downregulation of HER2, and enhancement of cytotoxicity using epirubicin in NSCLC cells. Mol Nutr Food Res 51:999–1005PubMedCrossRef
82.
83.
Sordella R, Bell DW, Haber DA, Settleman J (2004) Gefitinib-sensitizing EGFR mutations in lung cancer activate anti-apoptotic pathways. Science 305:1163–1167PubMedCrossRef
84.
Droogendijk HJ, Kluin-Nelemans HJ, van Doormaal JJ, Oranje AP, van de Loosdrecht AA, van Daele PL (2006) Imatinib mesylate in the treatment of systemic mastocytosis: a phase II trial. Cancer 107:345–351PubMedCrossRef
85.
Ramesh M, Ahlawat P, Srinivas NR (2010) Irinotecan and its active metabolite, SN-38: review of bioanalytical methods and recent update from clinical pharmacology perspectives. Biomed Chromatogr 24:104–123PubMedCrossRef
86.
Lu L, Payvandi F, Wu L, Zhang LH, Hariri RJ, Man HW et al (2009) The anti-cancer drug lenalidomide inhibits angiogenesis and metastasis via multiple inhibitory effects on endothelial cell function in normoxic and hypoxic conditions. Microvasc Res 77:78–86PubMedCrossRef
87.
Castellon E, Clementi M, Hitschfeld C, Sanchez C, Benitez D, Saenz L et al (2006) Effect of leuprolide and cetrorelix on cell growth, apoptosis, and GnRH receptor expression in primary cell cultures from human prostate carcinoma. Cancer Invest 24:261–268PubMedCrossRef
88.
Uga H, Kuramori C, Ohta A, Tsuboi Y, Tanaka H, Hatakeyama M et al (2006) A new mechanism of methotrexate action revealed by target screening with affinity beads. Mol Pharmacol 70:1832–1839PubMedCrossRef
89.
Wang Z, Chen Z, Yang S, Wang Y, Yu L, Zhang B et al (2012) (1)H NMR-based metabolomic analysis for identifying serum biomarkers to evaluate methotrexate treatment in patients with early rheumatoid arthritis. Exp Ther Med 4:165–171PubMedPubMedCentral
90.
Gan Y, Wientjes MG, Au JL (2006) Expression of basic fibroblast growth factor correlates with resistance to paclitaxel in human patient tumors. Pharm Res 23:1324–1331PubMedCrossRef
91.
Bowles JA, Wang SY, Link BK, Allan B, Beuerlein G, Campbell MA et al (2006) Anti-CD20 monoclonal antibody with enhanced affinity for CD16 activates NK cells at lower concentrations and more effectively than rituximab. Blood 108:2648–2654PubMedPubMedCentralCrossRef
92.
Tan AR, Swain SM (2003) Ongoing adjuvant trials with trastuzumab in breast cancer. Semin Oncol 30:54–64PubMedCrossRef
93.
Jordan MA, Kamath K (2007) How do microtubule-targeted drugs work? An overview. Curr Cancer Drug Targets 7:730–742PubMedCrossRef
94.
Schweizer MT, Antonarakis ES (2012) Abiraterone and other novel androgen-directed strategies for the treatment of prostate cancer: a new era of hormonal therapies is born. Ther Adv Urol 4:167–178PubMedPubMedCentralCrossRef
95.
Kluetz PG, Ning YM, Maher VE, Zhang L, Tang S, Ghosh D et al (2013) Abiraterone acetate in combination with prednisone for the treatment of patients with metastatic castration-resistant prostate cancer: U.S. Food and Drug Administration drug approval summary. Clin Cancer Res 19:6650–6656PubMedCrossRef
96.
Marbury T, Lawitz E, Stonerock R, Gonzalez M, Jiao J, Breeding J et al (2014) Single-dose pharmacokinetic studies of abiraterone acetate in men with hepatic or renal impairment. J Clin Pharmacol 54:732–741PubMedCrossRef
97.
Shaw AT, Engelman JA (2014) Ceritinib in ALK-rearranged non-small-cell lung cancer. N Engl J Med 370:2537–2539PubMedCrossRef
98.
Nishio M, Murakami H, Horiike A, Takahashi T, Hirai F, Suenaga N et al (2015) Phase I study of ceritinib (LDK378) in Japanese patients with advanced, anaplastic lymphoma kinase-rearranged non–small-cell lung canceror other tumors. J Thorac Oncol 10:1058–1066PubMedPubMedCentralCrossRef
99.
Peng B, Dutreix C, Mehring G, Hayes MJ, Ben-Am M, Seiberling M et al (2004) Absolute bioavailability of imatinib (Glivec) orally versus intravenous infusion. J Clin Pharmacol 44:158–162PubMedCrossRef
100.
Judson I, Ma P, Peng B, Verweij J, Racine A, di Paola ED et al (2005) Imatinib pharmacokinetics in patients with gastrointestinal stromal tumour: a retrospective population pharmacokinetic study over time. EORTC Soft Tissue and Bone Sarcoma Group. Cancer Chemother Pharmacol 55:379–386PubMedCrossRef
101.
Ramanathan RK, Egorin MJ, Takimoto CH, Remick SC, Doroshow JH, LoRusso PA et al (2008) Phase I and pharmacokinetic study of imatinib mesylate in patients with advanced malignancies and varying degrees of liver dysfunction: a study by the National Cancer Institute Organ Dysfunction Working Group. J Clin Oncol 26:563–569PubMedCrossRef
102.
Glare P, Aggarwal G, Clark K (2004) Ongoing controversies in the pharmacological management of cancer pain. Intern Med J 34:45–49PubMedCrossRef
103.
Lugo RA, Kern SE (2002) Clinical pharmacokinetics of morphine. J Pain Palliat Care Pharmacother 16:5–18PubMedCrossRef
104.
Hajiesmaeili MR, Safari S (2012) Pain management in the intensive care unit: do we need special protocols? Anesthesiol Pain Med 1:237–238CrossRef
105.
Nersesyan H, Slavin KV (2007) Current aproach to cancer pain management: availability and implications of different treatment options. Ther Clin Risk Manag 3:381–400PubMedPubMedCentral
106.
Terlinden R, Kogel BY, Englberger W, Tzschentke TM (2010) In vitro and in vivo characterization of tapentadol metabolites. Methods Find Exp Clin Pharmacol 32:31–38PubMedCrossRef
107.
Kneip C, Terlinden R, Beier H, Chen G (2008) Investigations into the drug–drug interaction potential of tapentadol in human liver microsomes and fresh human hepatocytes. Drug Metab Lett 2:67–75PubMedCrossRef
108.
Tzschentke TM, Christoph T, Kogel B, Schiene K, Hennies HH, Englberger W et al (2007) (-)-(1R,2R)-3-(3-dimethylamino-1-ethyl-2-methyl-propyl)-phenol hydrochloride (tapentadol HCl): a novel mu-opioid receptor agonist/norepinephrine reuptake inhibitor with broad-spectrum analgesic properties. J Pharmacol Exp Ther 323:265–276PubMedCrossRef
109.
Nagar S, Raffa RB (2008) Looking beyond the administered drug: metabolites of opioid analgesics. J Family Pract 57:S25–S32
110.
Xu XS, Smit JW, Lin R, Stuyckens K, Terlinden R, Nandy P (2010) Population pharmacokinetics of tapentadol immediate release (IR) in healthy subjects and patients with moderate or severe pain. Clin Pharmacokinet 49:671–682PubMedCrossRef
111.
112.
Hartrick C, Van Hove I, Stegmann J-U, Oh C, Upmalis D (2009) Efficacy and tolerability of tapentadol immediate release and oxycodone HCL immediate release in patients awaiting primary joint replacement surgery for end-stage joint disease: a ten-day, phase-3, randomized, double-blind-and placebo-controlled study. Clin Ther 31:260–271PubMedCrossRef
113.
Weinshilboum RM, Wang L (2006) Pharmacogenetics and pharmacogenomics: development, science, and translation. Annu Rev Genomics Hum Genet 7:223–245PubMedCrossRef
114.
Zhang A, Sun H, Wang P, Han Y, Wang X (2012) Modern analytical techniques in metabolomics analysis. Analyst 137:293–300PubMedCrossRef
115.
Dunn WB, Bailey NJ, Johnson HE (2005) Measuring the metabolome: current analytical technologies. Analyst 130:606–625PubMedCrossRef
116.
Mishur RJ, Rea SL (2012) Applications of mass spectrometry to metabolomics and metabonomics: detection of biomarkers of aging and of age-related diseases. Mass Spectrom Rev 31:70–95PubMedCrossRef
117.
Wang Z, Klipfell E, Bennett BJ, Koeth R, Levison BS, Dugar B et al (2011) Gut flora metabolism of phosphatidylcholine promotes cardiovascular disease. Nature 472:57–63PubMedPubMedCentralCrossRef
118.
Hernandez F, Ibanez M, Gracia-Lor E, Sancho JV (2011) Retrospective LC-QTOF-MS analysis searching for pharmaceutical metabolites in urban wastewater. J Sep Sci 34:3517–3526PubMedCrossRef
119.
Kalli A, Smith GT, Sweredoski MJ, Hess S (2013) Evaluation and optimization of mass spectrometric settings during data-dependent acquisition mode: focus on LTQ-Orbitrap mass analyzers. J Proteome Res 12:3071–3086PubMedPubMedCentralCrossRef
120.
Beaudry F, Le Blanc JC, Coutu M, Brown NK (1998) In vivo pharmacokinetic screening in cassette dosing experiments; the use of on-line prospekt liquid chromatography/atmospheric pressure chemical ionization tandem mass spectrometry technology in drug discovery. Rapid Commun Mass Spectrom 12:1216–1222PubMedCrossRef
121.
Xu N, Kim GE, Gregg H, Wagdy A, Swaine BA, Chang MS et al (2004) Automated 96-well liquid–liquid back extraction liquid chromatography–tandem mass spectrometry method for the determination of ABT-202 in human plasma. J Pharm Biomed Anal 36:189–195PubMedCrossRef
122.
Hsieh Y, Bryant MS, Brisson JM, Ng K, Korfmacher WA (2002) Direct cocktail analysis of drug discovery compounds in pooled plasma samples using liquid chromatography–tandem mass spectrometry. J Chromatogr B Analyt Technol Biomed Life Sci 767:353–362PubMedCrossRef
123.
Korfmacher WA, Cox KA, Ng KJ, Veals J, Hsieh Y, Wainhaus S et al (2001) Cassette-accelerated rapid rat screen: a systematic procedure for the dosing and liquid chromatography/atmospheric pressure ionization tandem mass spectrometric analysis of new chemical entities as part of new drug discovery. Rapid Commun Mass Spectrom 15:335–340PubMedCrossRef
124.
125.
Monte AA, Heard KJ, Vasiliou V (2012) Prediction of drug response and safety in clinical practice. J Med Toxicol 8:43–51PubMedCrossRef
126.
Dunn WB, Wilson ID, Nicholls AW, Broadhurst D (2012) The importance of experimental design and QC samples in large-scale and MS-driven untargeted metabolomic studies of humans. Bioanalysis 4:2249–2264PubMedCrossRef
127.
Lindon JC, Holmes E, Nicholson JK (2007) Metabonomics in pharmaceutical R&D. FEBS J 274:1140–1151PubMedCrossRef
128.
Idborg H, Edlund PO, Jacobsson SP (2004) Multivariate approaches for efficient detection of potential metabolites from liquid chromatography/mass spectrometry data. Rapid Commun Mass Spectrom 18:944–954PubMedCrossRef
129.
130.
Madsen R, Lundstedt T, Trygg J (2010) Chemometrics in metabolomics—a review in human disease diagnosis. Anal Chim Acta 659:23–33PubMedCrossRef
131.
Halouska S, Chacon O, Fenton RJ, Zinniel DK, Barletta RG, Powers R (2007) Use of NMR metabolomics to analyze the targets of d-cycloserine in mycobacteria: role of d-alanine racemase. J Proteome Res 6:4608–4614PubMedPubMedCentralCrossRef
132.
133.
Sugimoto M, Kawakami M, Robert M, Soga T, Tomita M (2012) Bioinformatics tools for mass spectroscopy-based metabolomic data processing and analysis. Curr Bioinform 7:96–108PubMedPubMedCentralCrossRef
134.
Roux A, Lison D, Junot C, Heilier JF (2011) Applications of liquid chromatography coupled to mass spectrometry-based metabolomics in clinical chemistry and toxicology: a review. Clin Biochem 44:119–135PubMedCrossRef
135.
Benhaim L, Labonte MJ, Lenz HJ (2012) Pharmacogenomics and metastatic colorectal cancer: current knowledge and perspectives. Scand J Gastroenterol 47:325–339PubMedCrossRef
136.
Backshall A, Sharma R, Clarke SJ, Keun HC (2011) Pharmacometabonomic profiling as a predictor of toxicity in patients with inoperable colorectal cancer treated with capecitabine. Clin Cancer Res 17:3019–3028PubMedCrossRef
137.
Nicholson JK, Everett JR, Lindon JC (2012) Longitudinal pharmacometabonomics for predicting patient responses to therapy: drug metabolism, toxicity and efficacy. Expert Opin Drug Metab Toxicol 8:135–139PubMedCrossRef
138.
Phapale PB, Kim SD, Lee HW, Lim M, Kale DD, Kim YL et al (2010) An integrative approach for identifying a metabolic phenotype predictive of individualized pharmacokinetics of tacrolimus. Clin Pharmacol Ther 87:426–436PubMedCrossRef
139.
Sha W, da Costa KA, Fischer LM, Milburn MV, Lawton KA, Berger A et al (2010) Metabolomic profiling can predict which humans will develop liver dysfunction when deprived of dietary choline. FASEB J 24:2962–2975PubMedPubMedCentralCrossRef
140.
Griffin JL, Vidal-Puig A (2008) Current challenges in metabolomics for diabetes research: a vital functional genomic tool or just a ploy for gaining funding? Physiol Genomics 34:1–5PubMedCrossRef
141.
Koal T, Deigner HP (2010) Challenges in mass spectrometry based targeted metabolomics. Curr Mol Med 10:216–226PubMedCrossRef
142.
Wei R (2011) Metabolomics and its practical value in pharmaceutical industry. Curr Drug Metab 12:345–358PubMedCrossRef
143.
Jentzmik F, Stephan C, Miller K, Schrader M, Erbersdobler A, Kristiansen G et al (2010) Sarcosine in urine after digital rectal examination fails as a marker in prostate cancer detection and identification of aggressive tumours. Eur Urol 58:12–18 (discussion 20-11) PubMedCrossRef
144.
Sreekumar A, Poisson LM, Rajendiran TM, Khan AP, Cao Q, Yu J et al (2009) Metabolomic profiles delineate potential role for sarcosine in prostate cancer progression. Nature 457:910–914PubMedPubMedCentralCrossRef
145.
Broadhurst DI, Kell DB (2006) Statistical strategies for avoiding false discoveries in metabolomics and related experiments. Metabolomics 2:171–196CrossRef
146.
Becquemont L, Alfirevic A, Amstutz U, Brauch H, Jacqz-Aigrain E, Laurent-Puig P et al (2011) Practical recommendations for pharmacogenomics-based prescription: 2010 ESF-UB conference on pharmacogenetics and pharmacogenomics. Pharmacogenomics 12:113–124PubMedCrossRef
147.
Kim MJ, Kim H, Cha IJ, Park JS, Shon JH, Liu KH et al (2005) High-throughput screening of inhibitory potential of nine cytochrome P450 enzymes in vitro using liquid chromatography/tandem mass spectrometry. Rapid Commun Mass Spectrom 19:2651–2658PubMedCrossRef
Metadata
Title
Pharmacokinetic variations in cancer patients with liver dysfunction: applications and challenges of pharmacometabolomics
Authors
Ali Aboel Dahab
Dhia El-Hag
Gamal M. Moutamed
Sarah Aboel Dahab
Ramadan Abuknesha
Norman W. Smith
Publication date
01-09-2016
Publisher
Springer Berlin Heidelberg
Published in
Cancer Chemotherapy and Pharmacology / Issue 3/2016
Print ISSN: 0344-5704
Electronic ISSN: 1432-0843
DOI
https://doi.org/10.1007/s00280-016-3028-4

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