Amlodipine metabolism in human liver microsomes and roles of CYP3A4/5 in the dihydropyridine dehydrogenation

Drug Metabolism and Disposition

Volumn 42, Issue 2, 2014, Pages 245-249

  Zhu, Yanlin ^a   Wang, Fen ^a   Li, Quan ^a   Zhu, Mingshe ^b   Du, Alicia ^a   Tang, Wei ^a   Chen, Weiqing ^a  

^a DMPK Department   (China)

^b BRISTOL MYERS SQUIBB   (United States)

Author keywords

[No Author keywords available]

Indexed keywords

ALPHA HYDROXYMIDAZOLAM; AMLODIPINE; BENZYLNIRVANOL; CYP3CIDE; CYTOCHROME P450 3A4; CYTOCHROME P450 3A5; CYTOCHROME P450 INHIBITOR; DIHYDROPYRIDINE; DRUG METABOLITE; FURAFYLLINE; KETOCONAZOLE; MIDAZOLAM; MONTELUKAST; PYRIDINE DERIVATIVE; QUINIDINE; SULFAPHENAZOLE; THIOTEPA; UNCLASSIFIED DRUG;

ARTICLE; CONTROLLED STUDY; DEALKYLATION; DEAMINATION; DEHYDROGENATION; DEMETHYLATION; DRUG CLEARANCE; DRUG METABOLISM; LIQUID CHROMATOGRAPHY; LIVER MICROSOME; MASS SPECTROMETRY; PHENOTYPE; PRIORITY JOURNAL; PROTEIN EXPRESSION; RACEMIC MIXTURE; STEREOISOMERISM;

AMLODIPINE; BIOTRANSFORMATION; CALCIUM CHANNEL BLOCKERS; CYTOCHROME P-450 CYP3A; DEALKYLATION; DEAMINATION; ENZYME INHIBITORS; HUMANS; MICROSOMES, LIVER; OXIDATION-REDUCTION; RECOMBINANT PROTEINS;

EID: 84891763726     PISSN: 00909556     EISSN: 1521009X     Source Type: Journal    
DOI: 10.1124/dmd.113.055400     Document Type: Article

References (18)

1. Abernethy DR (1991) Amlodipine: pharmacokinetic profile of a low-clearance calcium antagonist. J Cardiovasc Pharmacol 17 (Suppl 1):S4-S7.
2. Beresford AP, Macrae PV, and Stopher DA (1988b) Metabolism of amlodipine in the rat and the dog: a species difference. Xenobiotica 18:169-182. (Pubitemid 18071744)
3. Beresford AP, McGibney D, Humphrey MJ, Macrae PV, and Stopher DA (1988a) Metabolism and kinetics of amlodipine in man. Xenobiotica 18:245-254. (Pubitemid 18071751)
4. Bhatnagar V, Garcia EP, O'Connor DT, Brophy VH, Alcaraz J, Richard E, Bakris GL, Middleton JP, Norris KC, and Wright J, et al.; AASK Study Investigators (2010) CYP3A4 and CYP3A5 polymorphisms and blood pressure response to amlodipine among African-American men and women with early hypertensive renal disease. Am J Nephrol 31:95-103.
5. Christensen H, Hestad AL, Molden E, and Mathiesen L (2011) CYP3A5-mediated metabolism of midazolam in recombinant systems is highly sensitive to NADPH-cytochrome P450 reductase activity. Xenobiotica 41:1-5.
6. Faulkner JK, McGibney D, Chasseaud LF, Perry JL, and Taylor IW (1986) The pharmacokinetics of amlodipine in healthy volunteers after single intravenous and oral doses and after 14 repeated oral doses given once daily. Br J Clin Pharmacol 22:21-25. (Pubitemid 17177199)
7. Glesby MJ, Aberg JA, Kendall MA, Fichtenbaum CJ, Hafner R, Hall S, Grosskopf N, Zolopa AR, and Gerber JG; Adult AIDS Clinical Trials Group A5159 Protocol Team (2005) Pharmacokinetic interactions between indinavir plus ritonavir and calcium channel blockers. Clin Pharmacol Ther 78:143-153. (Pubitemid 41112282)
8. Guengerich FP, Brian WR, Iwasaki M, Sari MA, Bäärnhielm C, and Berntsson P (1991) Oxidation of dihydropyridine calcium channel blockers and analogues by human liver cytochrome P-450 IIIA4. J Med Chem 34:1838-1844.
9. Kim BH, Kim JR, Kim MG, Kim KP, Lee BY, Jang IJ, Shin SG, and Yu KS (2010) Pharmacodynamic (hemodynamic) and pharmacokinetic comparisons of S-amlodipine gentisate and racemate amlodipine besylate in healthy Korean male volunteers: two double-blind, randomized, two-period, two-treatment, two-sequence, double-dummy, single-dose crossover studies. Clin Ther 32:193-205.
10. Kim KA, Park PW, Lee OJ, Choi SH, Min BH, Shin KH, Chun BG, Shin JG, and Park JY (2006) Effect of CYP3A5*3 genotype on the pharmacokinetics and pharmacodynamics of amlodipine in healthy Korean subjects. Clin Pharmacol Ther 80:646-656. (Pubitemid 44920220)
11. Lee JE, van Heeswijk R, Alves K, Smith F, and Garg V (2011) Effect of the hepatitis C virus protease inhibitor telaprevir on the pharmacokinetics of amlodipine and atorvastatin. Antimicrob Agents Chemother 55:4569-4574.
12. Li X, Song X, Kamenecka TM, and Cameron MD (2012) Discovery of a highly selective CYP3A4 inhibitor suitable for reaction phenotyping studies and differentiation of CYP3A4 and CYP3A5. Drug Metab Dispos 40:1803-1809.
13. Stopher DA, Beresford AP, Macrae PV, and Humphrey MJ (1988) The metabolism and pharmacokinetics of amlodipine in humans and animals. J Cardiovasc Pharmacol 12 (Suppl 7): S55-S59. (Pubitemid 19014188)
14. Suchanova B, Kostiainen R, and Ketola RA (2008) Characterization of the in vitro metabolic profile of amlodipine in rat using liquid chromatography-mass spectrometry. Eur J Pharm Sci 33:91-99. (Pubitemid 350235195)
15. Suchanova B, Sispera L, and Wsol V (2006) Liquid chromatography-tandem mass spectrometry in chiral study of amlodipine biotransformation in rat hepatocytes. Anal Chim Acta 573-574: 273-283. (Pubitemid 44066971)
16. Walsky RL, Obach RS, Hyland R, Kang P, Zhou S, West M, Geoghegan KF, Helal CJ, Walker GS, and Goosen TC, et al. (2012) Selective mechanism-based inactivation of CYP3A4 by CYP3cide (PF-04981517) and its utility as an in vitro tool for delineating the relative roles of CYP3A4 versus CYP3A5 in the metabolism of drugs. Drug Metab Dispos 40:1686-1697.
17. Zhang YP, Zuo XC, Huang ZJ, Cai JJ, Wen J, Duan DD, and Yuan H (2013) CYP3A5 polymorphism, amlodipine and hypertension. J Hum Hypertens DOI: 10.1038/jhh.2013.67 [Epub ahead of print].
18. Zuo XC, Zhou YN, Zhang BK, Yang GP, Cheng ZN, Yuan H, Ouyang DS, Liu SK, Barrett JS, and Li PJ, et al. (2013) Effect of CYP3A5*3 polymorphism on pharmacokinetic drug interaction between tacrolimus and amlodipine. Drug Metab Pharmacokinet 28:398-405 Epub ahead of print.