Different effects of ketoconazole on the stereoselective first-pass metabolism of R/S-verapamil in the intestine and the liver: Important for the mechanistic understanding of first-pass drug-drug interactions

Drug Metabolism and Disposition

Volumn 37, Issue 11, 2009, Pages 2186-2196

  Thörn, Helena Anna ^a   Hedeland, Mikael ^a,b   Bondesson, Ulf ^a,b   Knutson, Lars ^c   Yasin, Mohammed ^d   Dickinson, Paul ^d   Lennernäs, Hans ^a  

^a UPPSALA UNIVERSITY   (Sweden)

^b NATIONAL VETERINARY INSTITUTE   (Sweden)

^c UPPSALA UNIVERSITY HOSPITAL   (Sweden)

^d ASTRAZENECA   (United Kingdom)

Author keywords

[No Author keywords available]

Indexed keywords

CYTOCHROME P450 3A; KETOCONAZOLE; NORVERAPAMIL; VERAPAMIL;

ANIMAL EXPERIMENT; AREA UNDER THE CURVE; ARTICLE; CONTINUOUS INFUSION; CONTROLLED STUDY; DRUG EFFECT; DRUG INHIBITION; ENANTIOMER; EXPERIMENTAL PIG; FEMALE; FIRST PASS EFFECT; HEPATIC VEIN; INTESTINE; LIQUID CHROMATOGRAPHY; LOW DRUG DOSE; MALE; MAXIMUM PLASMA CONCENTRATION; NONHUMAN; PORTAL VEIN; PRIORITY JOURNAL; STEREOCHEMISTRY; TANDEM MASS SPECTROMETRY;

ANIMALS; DRUG INTERACTIONS; FEMALE; INTESTINES; JEJUNUM; KETOCONAZOLE; LIVER; MALE; STEREOISOMERISM; SWINE; VERAPAMIL;

SUIDAE;

EID: 70350291953     PISSN: 00909556     EISSN: 1521009X     Source Type: Journal    
DOI: 10.1124/dmd.109.028027     Document Type: Article

References (36)

1. Anzenbacher P, Soucek P, Anzenbacherová E, Gut I, Hrubý K, Svoboda Z, and Květina J (1998) Presence and activity of cytochrome P450 isoforms in minipig liver microsomes: comparison with human liver samples. Drug Metab Dispos 26:56-59. (Pubitemid 28071325)
2. Bogaards JJ, Bertrand M, Jackson P, Oudshoorn MJ, Weaver RJ, van Bladeren PJ, and Walther B (2000) Determining the best animal model for human cytochrome P450 activities: a comparison of mouse, rat, rabbit, dog, micropig, monkey and man. Xenobiotica 30:1131-1152. (Pubitemid 32368013)
3. Busse D, Cosme J, Beaune P, Kroemer HK, and Eichelbaum M (1995) Cytochromes of the P450 2C subfamily are the major enzymes involved in the O-demethylation of verapamil in humans. Naunyn Schmiedebergs Arch Pharmacol 353:116-121. (Pubitemid 26009826)
4. 14C]verapamil in man. Drug Metab Dispos 7:145-148.
5. Engman H, Tannergren C, Artursson P, and Lennernäs H (2003) Enantioselective transport and CYP3A4-mediated metabolism of R/S-verapamil in Caco-2 cell monolayers. Eur J Pharm Sci 19:57-65. (Pubitemid 36506938)
6. Fagerholm U, Johansson M, and Lennernäs H (1996) Comparison between permeability coefficients in rat and human jejunum. Pharm Res 13:1336-1342. (Pubitemid 26344978)
7. Hanada K, Ikemi Y, Kukita K, Mihara K, and Ogata H (2008) Stereoselective first-pass metabolism of verapamil in the small intestine and liver in rats. Drug Metab Dispos 36:2037-2042.
8. Hedeland M, Fredriksson E, Lennernäs H, and Bondesson U (2004) Simultaneous quantification of the enantiomers of verapamil and its N-demethylated metabolite in human plasma using liquid chromatography-tandem mass spectrometry. J Chromatogr B Analyt Technol Biomed Life Sci 804:303-311. (Pubitemid 38481705)
9. Hinderling PH (1997) Red blood cells: a neglected compartment in pharmacokinetics and pharmacodynamics. Pharmacol Rev 49:279-295.
10. Kararli TT (1995) Comparison of the gastrointestinal anatomy, physiology, and biochemistry of humans and commonly used laboratory animals. Biopharm Drug Dispos 16:351-380.
11. Kolars JC, Awni WM, Merion RM, and Watkins PB (1991) First-pass metabolism of cyclosporin by the gut. Lancet 338:1488-1490.
12. Kroemer HK, Echizen H, Heidemann H, and Eichelbaum M (1992) Predictability of the in vivo metabolism of verapamil from in vitro data: contribution of individual metabolic pathways and stereoselective aspects. J Pharmacol Exp Ther 260:1052-1057.
13. Kroemer HK, Gautier JC, Beaune P, Henderson C, Wolf CR, and Eichelbaum M (1993) Identification of P450 enzymes involved in metabolism of verapamil in humans. Naunyn Schmiedebergs Arch Pharmacol 348:332-337. (Pubitemid 23271638)
14. Kunta JR, Lee SH, Perry BA, Lee YH, and Sinko PJ (2004) Differentiation of gut and hepatic first-pass loss of verapamil in intestinal and vascular access-ported (IVAP) rabbits. Drug Metab Dispos 32:1293-1298.
15. Lee YH, Perry BA, Lee HS, Kunta JR, Sutyak JP, and Sinko PJ (2001) Differentiation of gut and hepatic first-pass effect of drugs: 1. Studies of verapamil in ported dogs. Pharmacol Res 18:1721-1728.
16. Lennernäs H, Lee ID, Fagerholm U, and Amidon GL (1997) A residence-time distribution analysis of the hydrodynamics within the intestine in man during a regional single-pass perfusion with Loc-I-Gut: in-vivo permeability estimation. J Pharm Pharmacol 49:682-686. (Pubitemid 27341713)
17. Lillibridge JH, Liang BH, Kerr BM, Webber S, Quart B, Shetty BV, and Lee CA (1998) Characterization of the selectivity and mechanism of human cytochrome P450 inhibition by the human immunodeficiency virus-protease inhibitor nelfinavir mesylate. Drug Metab Dispos 26:609-616. (Pubitemid 28345843)
18. Mutlib AE and Nelson WL (1990) Synthesis and identification of the N-glucuronides of norgal-lopamil and norverapamil, unusual metabolites of gallopamil and verapamil. J Pharmacol Exp Ther 252:593-599.
19. Nordgren A, Karlsson T, and Wiklund L (2002) Glutamine concentration and tissue exchange with intravenously administered alpha-ketoglutaric acid and ammonium: a dose-response study in the pig. Nutrition 18:496-504 (Pubitemid 34586805)
20. Paine MF, Hart HL, Ludington SS, Haining RL, Rettie AE, and Zeldin DC (2006) The human intestinal cytochrome P450 "pie." Drug Metab Dispos 34:880-886.
21. Paine MF, Khalighi M, Fisher JM, Shen DD, Kunze KL, Marsh CL, Perkins JD, and Thummel KE (1997) Characterization of interintestinal and intraintestinal variations in human CYP3A-dependent metabolism. J Pharmacol Exp Ther 283:1552-1562. (Pubitemid 28016533)
22. Paine MF, Shen DD, Kunze KL, Perkins JD, Marsh CL, McVicar JP, Barr DM, Gillies BS, and Thummel KE (1996) First-pass metabolism of midazolam by the human intestine. Clin Pharmacol Ther 60:14-24.
23. Persson EM, Nordgren A, Forsell P, Knutson L, Ohgren C, Forssén S, Lennernäs H, and Abrahamsson B (2008) Improved understanding of the effect of food on drug absorption and bioavailability for lipophilic compounds using an intestinal pig perfusion model. Eur J Pharm Sci 34:22-29.
24. Petri N, Bergman E, Forsell P, Hedeland M, Bondesson U, Knutson L, and Lennernäs H (2006) First-pass effects of verapamil on the intestinal absorption and liver disposition of fexofenadine in the porcine model. Drug Metab Dispos 34:1182-1189. (Pubitemid 43920879)
25. Regårdh CG, Edgar B, Olsson R, Kendall M, Collste P, and Shansky C (1989) Pharmacokinetics of felodipine in patients with liver disease. Eur J Clin Pharmacol 36:473-479. (Pubitemid 19135210)
26. Rowland M and Tozer TN (1995) Clinical Pharmacokinetics Concepts and Applications, 3rd ed, Lippincott Williams & Wilkins, Philadelphia.
27. Sandström R, Karlsson A, Knutson L, and Lennernäs H (1998) Jejunal absorption and metabolism of R/S-verapamil in humans. Pharm Res 15:856-862.
28. Sandström R, Knutson TW, Knutson L, Jansson B, and Lennernäs H (1999) The effect of ketoconazole on the jejunal permeability and CYP3A metabolism of (R/S)-verapamil in humans. Br J Clin Pharmacol 48:180-189.
29. Shimada T, Yamazaki H, Mimura M, Inui Y, and Guengerich FP (1994) Interindividual variations in human liver cytochrome P-450 enzymes involved in the oxidation of drugs, carcinogens and toxic chemicals: studies with liver microsomes of 30 Japanese and 30 Caucasians. J Pharmacol Exp Ther 270:414-423. (Pubitemid 24229655)
30. Sjödin E, Fritsch H, Eriksson UG, Logren U, Nordgren A, Forsell P, Knutson L, and Lennernäs H (2008) Intestinal and hepatobiliary transport of ximelagatran and its metabolites in pigs. Drug Metab Dispos 36:1519-1528.
31. Skaanild MT (2006) Porcine cytochrome P450 and metabolism. Curr Pharm Des 12:1421-1427.
32. Skaanild MT and Friis C (1999) Cytochrome P450 sex differences in minipigs and conventional pigs. Pharmacol Toxicol 85:174-180.
33. Tannergren C, Engman H, Knutson L, Hedeland M, Bondesson U, and Lennernäs H (2004) St John's wort decreases the bioavailability of R- and S-verapamil through induction of the first-pass metabolism. Clin Pharmacol Ther 75:298-309. (Pubitemid 38471555)
34. Tracy TS, Korzekwa KR, Gonzalez FJ, and Wainer IW (1999) Cytochrome P450 isoforms involved in metabolism of the enantiomers of verapamil and norverapamil. Br J Clin Pharmacol 47:545-552. (Pubitemid 29199727)
35. Vogelgesang B, Echizen H, Schmidt E, and Eichelbaum M (1984) Stereoselective first-pass metabolism of highly cleared drugs: studies of the bioavailability of L- and D-verapamil examined with a stable isotope technique. Br J Clin Pharmacol 18:733-740. (Pubitemid 15209203)
36. von Richter O, Greiner B, Fromm MF, Fraser R, Omari T, Barclay ML, Dent J, Somogyi AA, and Eichelbaum M (2001) Determination of in vivo absorption, metabolism, and transport of drugs by the human intestinal wall and liver with a novel perfusion technique. Clin Pharmacol Ther 70:217-227. (Pubitemid 32868485)