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PMID: 8453961 Published · ppublish English Clinical Trial Journal Article Randomized Controlled Trial Research Support, Non-U.S. Gov't

Stereoselective pharmacokinetics of oral felodipine and nitrendipine in healthy subjects: correlation with nifedipine pharmacokinetics.

European journal of clinical pharmacology ·Vol. 44 ·No. 2 ·1993-00-00 ·Pages 163-9

Soons PA, Mulders TM, Uchida E, Schoemaker HC, Cohen AF, Breimer DD

Abstract

The pharmacokinetics of racemic (rac) felodipine, rac-nitrendipine and nifedipine (all given as an oral dose of 20 mg in solution) have been investigated in a randomised cross-over study in 12 healthy male subjects using stereoselective assays. Both felodipine and nitrendipine exhibited stereoselective pharmacokinetics. On average, the AUCs of the active (S)-enantiomers of felodipine and nitrendipine were 139% and 104% higher than those of their optical antipodes, but the elimination half-lives of the enantiomers of each racemate were not different. The AUCs of nifedipine, rac-felodipine, rac-nitrendipine and of their enantiomers were highly correlated (all r > 0.83), suggesting closely related rate limiting steps in the in vivo first-pass metabolism of these high-clearance drugs. Stereoselectivity was only a minor contributor to inter-individual variability in the oral pharmacokinetics of these compounds in healthy subjects.

MeSH Terms
Administration, Oral Adult Blood Proteins/metabolism Double-Blind Method Felodipine/blood,pharmacokinetics Half-Life Humans Male Nifedipine/blood,pharmacokinetics Nitrendipine/blood,pharmacokinetics Pyridines/metabolism Stereoisomerism
Chemicals
Blood Proteins Pyridines Nitrendipine Nifedipine Felodipine
Authors & Affiliations
6 authors, click to expand affiliations / ORCID
Soons P A
Center for Bio-Pharmaceutical Sciences, University of Leiden, The Netherlands.
Mulders T M
Uchida E
Schoemaker H C
Cohen A F
Breimer D D
References (40)
40 references, click to expand
  1. The trans-hepatic extraction of nifedipine.
    Br J Clin Pharmacol. 1987 Oct;24(4):473-7 PMID: 3689628
  2. Dihydropyridine receptor in rat brain labeled with [3H]nimodipine.
    Proc Natl Acad Sci U S A. 1983 Apr;80(8):2356-60 PMID: 6300912
  3. Analysis of nifedipine and its pyridine metabolite dehydronifedipine in blood and plasma: review and improved high-performance liquid chromatographic methodology.
    J Pharm Biomed Anal. 1991;9(6):475-84 PMID: 1747400
  4. Enantioselective determination of felodipine and other chiral dihydropyridine calcium entry blockers in human plasma.
    J Chromatogr. 1990 Jun 29;528(2):343-56 PMID: 2384574
  5. Serum binding of nifedipine and verapamil in patients with ischaemic heart disease on monotherapy.
    Br J Clin Pharmacol. 1989 Sep;28(3):357-61 PMID: 2789930
  6. The metabolism of nicardipine hydrochloride in healthy male volunteers.
    Xenobiotica. 1986 Apr;16(4):341-9 PMID: 3716455
  7. Gas chromatographic analysis of nitrendipine and its pyridine metabolite in human plasma.
    J Chromatogr. 1988 Jul 15;428(2):362-8 PMID: 3215939
  8. Elimination and haemodynamic effects of nitrendipine in patients with chronic renal failure.
    Eur J Clin Pharmacol. 1989;36(5):433-7 PMID: 2753062
  9. Cytochrome P-450-catalyzed dehydrogenation of 1,4-dihydropyridines.
    J Biol Chem. 1988 Jun 15;263(17):8168-75 PMID: 3372517
  10. Inter- and intra-subject variability of nitrendipine and the effects of food.
    Eur J Clin Pharmacol. 1987;32(4):357-60 PMID: 3609113
  11. High-performance liquid chromatography of the metabolites of nitrendipine and investigation into the metabolic pathways of this dihydropyridine.
    J Chromatogr. 1990 Aug 24;530(1):206-11 PMID: 2277114
  12. Plasma levels of (+)- and (-)-nilvadipine after oral dosing with racemic (+)-nilvadipine in man.
    Res Commun Chem Pathol Pharmacol. 1987 Aug;57(2):229-37 PMID: 3659571
  13. A population study of the pharmacokinetics of felodipine.
    Br J Clin Pharmacol. 1991 Jan;31(1):15-24 PMID: 2015166
  14. Oxidation of dihydropyridine calcium channel blockers and analogues by human liver cytochrome P-450 IIIA4.
    J Med Chem. 1991 Jun;34(6):1838-44 PMID: 2061924
  15. Clinical pharmacokinetics of felodipine. A summary.
    Drugs. 1987;34 Suppl 3:16-27 PMID: 3327676
  16. A 'cocktail' strategy to assess in vivo oxidative drug metabolism in humans.
    Trends Pharmacol Sci. 1990 Jun;11(6):223-5 PMID: 2200179
  17. Stereoselective pharmacokinetics of oral and intravenous nitrendipine in healthy male subjects.
    Br J Clin Pharmacol. 1991 Jul;32(1):11-6 PMID: 1888628
  18. Stereoselective oxidation and plasma protein binding of nilvadipine, a new dihydropyridine calcium antagonist, in man.
    Res Commun Chem Pathol Pharmacol. 1988 May;60(2):161-72 PMID: 3393731
  19. Pharmacokinetics of nisoldipine. III. Biotransformation of nisoldipine in rat, dog, monkey, and man.
    Arzneimittelforschung. 1988 Aug;38(8):1105-10 PMID: 2973788
  20. Serum concentrations and effects of (+/-)-nicardipine compared with nifedipine in a population of healthy subjects.
    Clin Pharmacol Ther. 1990 Aug;48(2):155-60 PMID: 2199131
  21. Protein binding of nifedipine.
    J Pharm Pharmacol. 1986 May;38(5):399-400 PMID: 2872322
  22. The contribution of nisoldipine-induced changes in liver blood flow to its pharmacokinetics after oral administration.
    Br J Clin Pharmacol. 1989 May;27(5):581-6 PMID: 2757881
  23. Variability in the pharmacokinetics of nisoldipine as caused by differences in liver blood flow response.
    J Clin Pharmacol. 1989 Aug;29(8):714-21 PMID: 2778091
  24. Total and free steady-state plasma levels and pharmacokinetics of nifedipine in patients with terminal renal failure.
    Eur J Clin Pharmacol. 1989;37(2):185-9 PMID: 2792174
  25. Standardization of symbols in clinical pharmacology.
    Eur J Clin Pharmacol. 1988;35(1):1-7 PMID: 3220089
  26. Cytochrome P-450-dependent oxidation of felodipine--a 1,4-dihydropyridine--to the corresponding pyridine.
    Xenobiotica. 1984 Sep;14(9):719-26 PMID: 6516445
  27. The intra- and inter-subject variability of nifedipine pharmacokinetics in young volunteers.
    Eur J Clin Pharmacol. 1986;30(1):57-60 PMID: 3709633
  28. Application of stable isotope methodology to study the pharmacokinetics, bioavailability and metabolism of nitrendipine after i.v. and p.o. administration.
    Br J Clin Pharmacol. 1987 Nov;24(5):561-9 PMID: 3435690
  29. Oral absorption profile of nitrendipine in healthy subjects: a kinetic and dynamic study.
    Br J Clin Pharmacol. 1989 Feb;27(2):179-89 PMID: 2713213
  30. Contribution of the intestine to the first-pass metabolism of felodipine in the rat.
    J Pharmacol Exp Ther. 1989 Aug;250(2):632-6 PMID: 2760845
  31. Pharmacokinetics of nitrendipine in terminal renal failure.
    Eur J Clin Pharmacol. 1989;36(5):467-71 PMID: 2753064
  32. Stereoselective inhibition of thromboxane-induced coronary vasoconstriction by 1,4-dihydropyridine calcium channel antagonists.
    Chirality. 1990;2(4):233-40 PMID: 1964575
  33. [The binding of 4-(2'-nitrophenyl)-2,6-dimethyl-1,4-dihydropyridine-3,5-dicarboxylic acid dimethyl ester (nifedipine) as well as other coronary active substances to serum albumins].
    Arzneimittelforschung. 1974 Apr;24(4):455-66 PMID: 4211693
  34. Mechanism-based inactivation of human liver microsomal cytochrome P-450 IIIA4 by gestodene.
    Chem Res Toxicol. 1990 Jul-Aug;3(4):363-71 PMID: 2133086
  35. Oxidation of 4-aryl- and 4-alkyl-substituted 2,6-dimethyl-3,5-bis(alkoxycarbonyl)-1,4-dihydropyridines by human liver microsomes and immunochemical evidence for the involvement of a form of cytochrome P-450.
    J Med Chem. 1986 Sep;29(9):1596-603 PMID: 3746811
  36. Nifedipine. A review of its pharmacodynamic and pharmacokinetic properties, and therapeutic efficacy, in ischaemic heart disease, hypertension and related cardiovascular disorders.
    Drugs. 1985 Sep;30(3):182-274 PMID: 2412780
  37. Characterization of rat and human liver microsomal cytochrome P-450 forms involved in nifedipine oxidation, a prototype for genetic polymorphism in oxidative drug metabolism.
    J Biol Chem. 1986 Apr 15;261(11):5051-60 PMID: 3514607
  38. Characterization of human microsomal cytochrome P-450 enzymes.
    Annu Rev Pharmacol Toxicol. 1989;29:241-64 PMID: 2658771
  39. Variability in nifedipine pharmacokinetics and dynamics: a new oxidation polymorphism in man.
    Biochem Pharmacol. 1984 Nov 15;33(22):3721-4 PMID: 6508829
  40. Nifedipine: influence of renal function on pharmacokinetic/hemodynamic relationship.
    Clin Pharmacol Ther. 1985 May;37(5):563-74 PMID: 3987180
Article Info
Journal
European journal of clinical pharmacology
Abbr.
Eur J Clin Pharmacol
ISSN
0031-6970
DOI
10.1007/BF00315475
Published
1993-00-00
Pages
163-9
Language
English
Region
Germany
NLM ID
1256165
Subset
IM
External Links
PubMed source DOI: 10.1007/BF00315475 View journal details
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