Skip to main content
Top
Published in: BMC Clinical Pharmacology 1/2006

Open Access 01-12-2006 | Research article

Single and multiple dose pharmacokinetics of maritime pine bark extract (Pycnogenol) after oral administration to healthy volunteers

Authors: Tanja Grimm, Roswitha Skrabala, Zuzana Chovanová, Jana Muchová, Katarína Sumegová, Anna Liptáková, Zdeňka Ďuračková, Petra Högger

Published in: BMC Clinical Pharmacology | Issue 1/2006

Login to get access

Abstract

Background

Since plant extracts are increasingly used as phytotherapeutics or dietary supplements information on bioavailability, bioefficacy and safety are warranted. We elucidated the plasma kinetics of genuine extract components and metabolites after single and multiple ingestion of the standardized maritime pine bark extract Pycnogenol (USP quality) by human volunteers.

Methods

Eleven volunteers received a single dose of 300 mg pine bark extract, five volunteers ingested 200 mg daily for five days to reach steady state concentrations. Plasma samples were obtained before and at defined time points after intake of the extract. Samples were analyzed by HPLC with ion-pair reagents and simultaneous UV and electrochemical detection.

Results

We quantified total plasma concentrations of catechin, caffeic acid, ferulic acid, taxifolin and the metabolite M1 (δ-(3,4-dihydroxy-phenyl)-γ-valerolactone). Additionally, we describe plasma time courses and steady state appearance of ten so far unknown compounds, U1 to U10. After single ingestion, compounds derived from the extract were rapidly absorbed and the majority of them were detectable over whole experimental period of 14 h. The analysis of steady state plasma samples revealed significant phase II metabolism.

Conclusion

We present the first systematic pharmacokinetic analysis of compounds derived from maritime pine bark extract. Beyond the known constituents and metabolites we uncovered the plasma time courses of ten unknown compounds. In concert with our previous detection of anti-inflammatory bioefficacy of these plasma samples ex vivo we suggest that constituents and metabolites of Pycnogenol bear potential for disclosure of novel active principles.
Appendix
Available only for authorised users
Literature
1.
go back to reference Gurley BJ, Gardner SF, Hubbard MA, Williams DK, Gentry WB, Carrier J, Khan IA, Edwards DJ, Shah A: In vivo assessment of botanical supplementation on human cytochrome P450 phenotypes: Citrus aurantium, Echinacea purpurea, milk thistle, and saw palmetto. Clin Pharmacol Ther. 2004, 76: 428-440. 10.1016/j.clpt.2004.07.007.CrossRefPubMed Gurley BJ, Gardner SF, Hubbard MA, Williams DK, Gentry WB, Carrier J, Khan IA, Edwards DJ, Shah A: In vivo assessment of botanical supplementation on human cytochrome P450 phenotypes: Citrus aurantium, Echinacea purpurea, milk thistle, and saw palmetto. Clin Pharmacol Ther. 2004, 76: 428-440. 10.1016/j.clpt.2004.07.007.CrossRefPubMed
2.
go back to reference Rengelshausen J, Banfield M, Riedel KD, Burhenne J, Weiss J, Thomsen T, Walter-Sack I, Haefeli WE, Mikus G: Opposite effects of short-term and long-term St John's wort intake on voriconazole pharmacokinetics. Clin Pharmacol Ther. 2005, 78: 25-33. 10.1016/j.clpt.2005.01.024.CrossRefPubMed Rengelshausen J, Banfield M, Riedel KD, Burhenne J, Weiss J, Thomsen T, Walter-Sack I, Haefeli WE, Mikus G: Opposite effects of short-term and long-term St John's wort intake on voriconazole pharmacokinetics. Clin Pharmacol Ther. 2005, 78: 25-33. 10.1016/j.clpt.2005.01.024.CrossRefPubMed
3.
go back to reference Williamson G, Manach C: Bioavailability and bioefficacy of polyphenols in humans. II. Review of 93 intervention studies. Am J Clin Nutr. 2005, 81: 243S-255S.PubMed Williamson G, Manach C: Bioavailability and bioefficacy of polyphenols in humans. II. Review of 93 intervention studies. Am J Clin Nutr. 2005, 81: 243S-255S.PubMed
4.
go back to reference Liu JP, Zhang M, Wang WY, Grimsgaard S: Chinese herbal medicines for type 2 diabetes mellitus. Cochrane Database Syst Rev. 2004, CD003642- Liu JP, Zhang M, Wang WY, Grimsgaard S: Chinese herbal medicines for type 2 diabetes mellitus. Cochrane Database Syst Rev. 2004, CD003642-
5.
go back to reference Manach C, Williamson G, Morand C, Scalbert A, Remesy C: Bioavailability and bioefficacy of polyphenols in humans. I. Review of 97 bioavailability studies. Am J Clin Nutr. 2005, 81: 230S-242S.PubMed Manach C, Williamson G, Morand C, Scalbert A, Remesy C: Bioavailability and bioefficacy of polyphenols in humans. I. Review of 97 bioavailability studies. Am J Clin Nutr. 2005, 81: 230S-242S.PubMed
6.
go back to reference Wittemer SM, Ploch M, Windeck T, Muller SC, Drewelow B, Derendorf H, Veit M: Bioavailability and pharmacokinetics of caffeoylquinic acids and flavonoids after oral administration of Artichoke leaf extracts in humans. Phytomedicine. 2005, 12: 28-38. 10.1016/j.phymed.2003.11.002.CrossRefPubMed Wittemer SM, Ploch M, Windeck T, Muller SC, Drewelow B, Derendorf H, Veit M: Bioavailability and pharmacokinetics of caffeoylquinic acids and flavonoids after oral administration of Artichoke leaf extracts in humans. Phytomedicine. 2005, 12: 28-38. 10.1016/j.phymed.2003.11.002.CrossRefPubMed
7.
go back to reference Loew D, Schrodter A, Schwankl W, Marz RW: Measurement of the bioavailability of aescin-containing extracts. Methods Find Exp Clin Pharmacol. 2000, 22: 537-542.PubMed Loew D, Schrodter A, Schwankl W, Marz RW: Measurement of the bioavailability of aescin-containing extracts. Methods Find Exp Clin Pharmacol. 2000, 22: 537-542.PubMed
8.
go back to reference Schulz HU, Schurer M, Bassler D, Weiser D: Investigation of the bioavailability of hypericin, pseudohypericin, hyperforin and the flavonoids quercetin and isorhamnetin following single and multiple oral dosing of a hypericum extract containing tablet. Arzneimittelforschung. 2005, 55: 15-22.PubMed Schulz HU, Schurer M, Bassler D, Weiser D: Investigation of the bioavailability of hypericin, pseudohypericin, hyperforin and the flavonoids quercetin and isorhamnetin following single and multiple oral dosing of a hypericum extract containing tablet. Arzneimittelforschung. 2005, 55: 15-22.PubMed
9.
go back to reference Vuksan V, Sievenpiper JL: Herbal remedies in the management of diabetes: lessons learned from the study of ginseng. Nutr Metab Cardiovasc Dis. 2005, 15: 149-160. 10.1016/j.numecd.2005.05.001.CrossRefPubMed Vuksan V, Sievenpiper JL: Herbal remedies in the management of diabetes: lessons learned from the study of ginseng. Nutr Metab Cardiovasc Dis. 2005, 15: 149-160. 10.1016/j.numecd.2005.05.001.CrossRefPubMed
10.
go back to reference Maritime Pine Extract. United States Pharmacopeia. 2005, Rockville, United States Pharmacopeial Convention, Inc., 28: 2115-2116. Maritime Pine Extract. United States Pharmacopeia. 2005, Rockville, United States Pharmacopeial Convention, Inc., 28: 2115-2116.
11.
go back to reference Rohdewald P: A review of the French maritime pine bark extract (Pycnogenol), a herbal medication with a diverse clinical pharmacology. Int J Clin Pharmacol Ther. 2002, 40: 158-168.CrossRefPubMed Rohdewald P: A review of the French maritime pine bark extract (Pycnogenol), a herbal medication with a diverse clinical pharmacology. Int J Clin Pharmacol Ther. 2002, 40: 158-168.CrossRefPubMed
12.
go back to reference Belcaro G, Cesarone MR, Errichi BM, Ledda A, Di Renzo A, Stuard S, Dugall M, Pellegrini L, Rohdewald P, Ippolito E, Ricci A, Cacchio M, Ruffini I, Fano F, Hosoi M: Venous ulcers: microcirculatory improvement and faster healing with local use of pycnogenol((r)). Angiology. 2005, 56: 699-705. 10.1177/000331970505600407.CrossRefPubMed Belcaro G, Cesarone MR, Errichi BM, Ledda A, Di Renzo A, Stuard S, Dugall M, Pellegrini L, Rohdewald P, Ippolito E, Ricci A, Cacchio M, Ruffini I, Fano F, Hosoi M: Venous ulcers: microcirculatory improvement and faster healing with local use of pycnogenol((r)). Angiology. 2005, 56: 699-705. 10.1177/000331970505600407.CrossRefPubMed
13.
go back to reference Hosseini S, Pishnamazi S, Sadrzadeh SM, Farid F, Farid R, Watson RR: Pycnogenol((R)) in the Management of Asthma. J Med Food. 2001, 4: 201-209. 10.1089/10966200152744472.CrossRefPubMed Hosseini S, Pishnamazi S, Sadrzadeh SM, Farid F, Farid R, Watson RR: Pycnogenol((R)) in the Management of Asthma. J Med Food. 2001, 4: 201-209. 10.1089/10966200152744472.CrossRefPubMed
14.
go back to reference Lau BH, Riesen SK, Truong KP, Lau EW, Rohdewald P, Barreta RA: Pycnogenol as an adjunct in the management of childhood asthma. J Asthma. 2004, 41: 825-832. 10.1081/JAS-200038433.CrossRefPubMed Lau BH, Riesen SK, Truong KP, Lau EW, Rohdewald P, Barreta RA: Pycnogenol as an adjunct in the management of childhood asthma. J Asthma. 2004, 41: 825-832. 10.1081/JAS-200038433.CrossRefPubMed
15.
go back to reference Düweler KG, Rohdewald P: Urinary metabolites of French maritime pine bark extract in humans. Pharmazie. 2000, 55: 364-368.PubMed Düweler KG, Rohdewald P: Urinary metabolites of French maritime pine bark extract in humans. Pharmazie. 2000, 55: 364-368.PubMed
16.
go back to reference Virgili F, Pagana G, Bourne L, Rimbach G, Natella F, Rice-Evans C, Packer L: Ferulic acid excretion as a marker of consumption of a French maritime pine (Pinus maritima) bark extract. Free Radic Biol Med. 2000, 28: 1249-1256. 10.1016/S0891-5849(00)00244-6.CrossRefPubMed Virgili F, Pagana G, Bourne L, Rimbach G, Natella F, Rice-Evans C, Packer L: Ferulic acid excretion as a marker of consumption of a French maritime pine (Pinus maritima) bark extract. Free Radic Biol Med. 2000, 28: 1249-1256. 10.1016/S0891-5849(00)00244-6.CrossRefPubMed
17.
go back to reference Das NP: Studies on flavonoid metabolism. Absorption and metabolism of (+)-catechin in man. Biochem Pharmacol. 1971, 20: 3435-3445. 10.1016/0006-2952(71)90449-7.CrossRefPubMed Das NP: Studies on flavonoid metabolism. Absorption and metabolism of (+)-catechin in man. Biochem Pharmacol. 1971, 20: 3435-3445. 10.1016/0006-2952(71)90449-7.CrossRefPubMed
18.
go back to reference Lipinski CA, Lombardo F, Dominy BW, Feeney PJ: Experimental and computational approaches to estimate solubility and permeability in drug discovery and development settings. Adv Drug Deliv Rev. 2001, 46: 3-26. 10.1016/S0169-409X(00)00129-0.CrossRefPubMed Lipinski CA, Lombardo F, Dominy BW, Feeney PJ: Experimental and computational approaches to estimate solubility and permeability in drug discovery and development settings. Adv Drug Deliv Rev. 2001, 46: 3-26. 10.1016/S0169-409X(00)00129-0.CrossRefPubMed
19.
go back to reference Donovan JL, Bell JR, Kasim-Karakas S, German JB, Walzem RL, Hansen RJ, Waterhouse AL: Catechin is present as metabolites in human plasma after consumption of red wine. J Nutr. 1999, 129: 1662-1668.PubMed Donovan JL, Bell JR, Kasim-Karakas S, German JB, Walzem RL, Hansen RJ, Waterhouse AL: Catechin is present as metabolites in human plasma after consumption of red wine. J Nutr. 1999, 129: 1662-1668.PubMed
20.
go back to reference Bell JR, Donovan JL, Wong R, Waterhouse AL, German JB, Walzem RL, Kasim-Karakas SE: (+)-Catechin in human plasma after ingestion of a single serving of reconstituted red wine. Am J Clin Nutr. 2000, 71: 103-108.PubMed Bell JR, Donovan JL, Wong R, Waterhouse AL, German JB, Walzem RL, Kasim-Karakas SE: (+)-Catechin in human plasma after ingestion of a single serving of reconstituted red wine. Am J Clin Nutr. 2000, 71: 103-108.PubMed
21.
go back to reference Hackett AM, Griffiths LA, Broillet A, Wermeille M: The metabolism and excretion of (+)-[14C]cyanidanol-3 in man following oral administration. Xenobiotica. 1983, 13: 279-286.CrossRefPubMed Hackett AM, Griffiths LA, Broillet A, Wermeille M: The metabolism and excretion of (+)-[14C]cyanidanol-3 in man following oral administration. Xenobiotica. 1983, 13: 279-286.CrossRefPubMed
22.
go back to reference Goldberg DM, Yan J, Soleas GJ: Absorption of three wine-related polyphenols in three different matrices by healthy subjects. Clin Biochem. 2003, 36: 79-87. 10.1016/S0009-9120(02)00397-1.CrossRefPubMed Goldberg DM, Yan J, Soleas GJ: Absorption of three wine-related polyphenols in three different matrices by healthy subjects. Clin Biochem. 2003, 36: 79-87. 10.1016/S0009-9120(02)00397-1.CrossRefPubMed
23.
go back to reference Caccetta RA, Croft KD, Beilin LJ, Puddey IB: Ingestion of red wine significantly increases plasma phenolic acid concentrations but does not acutely affect ex vivo lipoprotein oxidizability. Am J Clin Nutr. 2000, 71: 67-74.PubMed Caccetta RA, Croft KD, Beilin LJ, Puddey IB: Ingestion of red wine significantly increases plasma phenolic acid concentrations but does not acutely affect ex vivo lipoprotein oxidizability. Am J Clin Nutr. 2000, 71: 67-74.PubMed
24.
go back to reference Simonetti P, Gardana C, Pietta P: Caffeic acid as biomarker of red wine intake. Methods Enzymol. 2001, 335: 122-130.CrossRefPubMed Simonetti P, Gardana C, Pietta P: Caffeic acid as biomarker of red wine intake. Methods Enzymol. 2001, 335: 122-130.CrossRefPubMed
25.
go back to reference Nardini M, Cirillo E, Natella F, Scaccini C: Absorption of phenolic acids in humans after coffee consumption. J Agric Food Chem. 2002, 50: 5735-5741. 10.1021/jf0257547.CrossRefPubMed Nardini M, Cirillo E, Natella F, Scaccini C: Absorption of phenolic acids in humans after coffee consumption. J Agric Food Chem. 2002, 50: 5735-5741. 10.1021/jf0257547.CrossRefPubMed
26.
go back to reference Nardini M, Natella F, Scaccini C, Ghiselli A: Phenolic acids from beer are absorbed and extensively metabolized in humans. J Nutr Biochem. 2006, 17: 14-22. 10.1016/j.jnutbio.2005.03.026.CrossRefPubMed Nardini M, Natella F, Scaccini C, Ghiselli A: Phenolic acids from beer are absorbed and extensively metabolized in humans. J Nutr Biochem. 2006, 17: 14-22. 10.1016/j.jnutbio.2005.03.026.CrossRefPubMed
27.
go back to reference Kern SM, Bennett RN, Mellon FA, Kroon PA, Garcia-Conesa MT: Absorption of hydroxycinnamates in humans after high-bran cereal consumption. J Agric Food Chem. 2003, 51: 6050-6055. 10.1021/jf0302299.CrossRefPubMed Kern SM, Bennett RN, Mellon FA, Kroon PA, Garcia-Conesa MT: Absorption of hydroxycinnamates in humans after high-bran cereal consumption. J Agric Food Chem. 2003, 51: 6050-6055. 10.1021/jf0302299.CrossRefPubMed
28.
go back to reference Schoefer L, Mohan R, Schwiertz A, Braune A, Blaut M: Anaerobic degradation of flavonoids by Clostridium orbiscindens. Appl Environ Microbiol. 2003, 69: 5849-5854. 10.1128/AEM.69.10.5849-5854.2003.CrossRefPubMedPubMedCentral Schoefer L, Mohan R, Schwiertz A, Braune A, Blaut M: Anaerobic degradation of flavonoids by Clostridium orbiscindens. Appl Environ Microbiol. 2003, 69: 5849-5854. 10.1128/AEM.69.10.5849-5854.2003.CrossRefPubMedPubMedCentral
29.
go back to reference Li C, Lee MJ, Sheng S, Meng X, Prabhu S, Winnik B, Huang B, Chung JY, Yan S, Ho CT, Yang CS: Structural identification of two metabolites of catechins and their kinetics in human urine and blood after tea ingestion. Chem Res Toxicol. 2000, 13: 177-184. 10.1021/tx9901837.CrossRefPubMed Li C, Lee MJ, Sheng S, Meng X, Prabhu S, Winnik B, Huang B, Chung JY, Yan S, Ho CT, Yang CS: Structural identification of two metabolites of catechins and their kinetics in human urine and blood after tea ingestion. Chem Res Toxicol. 2000, 13: 177-184. 10.1021/tx9901837.CrossRefPubMed
30.
go back to reference Lee MJ, Maliakal P, Chen L, Meng X, Bondoc FY, Prabhu S, Lambert G, Mohr S, Yang CS: Pharmacokinetics of tea catechins after ingestion of green tea and (-)-epigallocatechin-3-gallate by humans: formation of different metabolites and individual variability. Cancer Epidemiol Biomarkers Prev. 2002, 11: 1025-1032.PubMed Lee MJ, Maliakal P, Chen L, Meng X, Bondoc FY, Prabhu S, Lambert G, Mohr S, Yang CS: Pharmacokinetics of tea catechins after ingestion of green tea and (-)-epigallocatechin-3-gallate by humans: formation of different metabolites and individual variability. Cancer Epidemiol Biomarkers Prev. 2002, 11: 1025-1032.PubMed
31.
go back to reference Sano A, Yamakoshi J, Tokutake S, Tobe K, Kubota Y, Kikuchi M: Procyanidin B1 is detected in human serum after intake of proanthocyanidin-rich grape seed extract. Biosci Biotechnol Biochem. 2003, 67: 1140-1143. 10.1271/bbb.67.1140.CrossRefPubMed Sano A, Yamakoshi J, Tokutake S, Tobe K, Kubota Y, Kikuchi M: Procyanidin B1 is detected in human serum after intake of proanthocyanidin-rich grape seed extract. Biosci Biotechnol Biochem. 2003, 67: 1140-1143. 10.1271/bbb.67.1140.CrossRefPubMed
32.
go back to reference Grimm T, Schäfer A, Högger P: Antioxidant activity and inhibition of matrix metalloproteinases by metabolites of maritime pine bark extract (pycnogenol). Free Radic Biol Med. 2004, 36: 811-822. 10.1016/j.freeradbiomed.2003.12.017.CrossRefPubMed Grimm T, Schäfer A, Högger P: Antioxidant activity and inhibition of matrix metalloproteinases by metabolites of maritime pine bark extract (pycnogenol). Free Radic Biol Med. 2004, 36: 811-822. 10.1016/j.freeradbiomed.2003.12.017.CrossRefPubMed
33.
go back to reference Koga T, Meydani M: Effect of plasma metabolites of (+)-catechin and quercetin on monocyte adhesion to human aortic endothelial cells. Am J Clin Nutr. 2001, 73: 941-948.PubMed Koga T, Meydani M: Effect of plasma metabolites of (+)-catechin and quercetin on monocyte adhesion to human aortic endothelial cells. Am J Clin Nutr. 2001, 73: 941-948.PubMed
34.
go back to reference Moon JH, Tsushida T, Nakahara K, Terao J: Identification of quercetin 3-O-beta-D-glucuronide as an antioxidative metabolite in rat plasma after oral administration of quercetin. Free Radic Biol Med. 2001, 30: 1274-1285. 10.1016/S0891-5849(01)00522-6.CrossRefPubMed Moon JH, Tsushida T, Nakahara K, Terao J: Identification of quercetin 3-O-beta-D-glucuronide as an antioxidative metabolite in rat plasma after oral administration of quercetin. Free Radic Biol Med. 2001, 30: 1274-1285. 10.1016/S0891-5849(01)00522-6.CrossRefPubMed
35.
go back to reference Schäfer A, Chovanova Z, Muchova J, Sumegova K, Liptakova A, Durackova Z, Högger P: Inhibition of COX-1 and COX-2 activity by plasma of human volunteers after ingestion of French maritime pine bark extract (Pycnogenol). Biomed Pharmacother. 2006, 60: 5-9. 10.1016/j.biopha.2005.08.006.CrossRefPubMed Schäfer A, Chovanova Z, Muchova J, Sumegova K, Liptakova A, Durackova Z, Högger P: Inhibition of COX-1 and COX-2 activity by plasma of human volunteers after ingestion of French maritime pine bark extract (Pycnogenol). Biomed Pharmacother. 2006, 60: 5-9. 10.1016/j.biopha.2005.08.006.CrossRefPubMed
36.
go back to reference Grimm T, Chovanova Z, Muchova J, Sumegova K, Liptakova A, Durackova Z, Högger P: Inhibition of NF-kappaB activation and MMP-9 secretion by plasma of human volunteers after ingestion of maritime pine bark extract (Pycnogenol). J Inflamm (Lond). 2006, 3: 1-CrossRef Grimm T, Chovanova Z, Muchova J, Sumegova K, Liptakova A, Durackova Z, Högger P: Inhibition of NF-kappaB activation and MMP-9 secretion by plasma of human volunteers after ingestion of maritime pine bark extract (Pycnogenol). J Inflamm (Lond). 2006, 3: 1-CrossRef
Metadata
Title
Single and multiple dose pharmacokinetics of maritime pine bark extract (Pycnogenol) after oral administration to healthy volunteers
Authors
Tanja Grimm
Roswitha Skrabala
Zuzana Chovanová
Jana Muchová
Katarína Sumegová
Anna Liptáková
Zdeňka Ďuračková
Petra Högger
Publication date
01-12-2006
Publisher
BioMed Central
Published in
BMC Clinical Pharmacology / Issue 1/2006
Electronic ISSN: 1472-6904
DOI
https://doi.org/10.1186/1472-6904-6-4

Other articles of this Issue 1/2006

BMC Clinical Pharmacology 1/2006 Go to the issue