Stereoselective pharmacokinetics and pharmacodynamics of verapamil and norverapamil in rabbits

Y. Mori, K. Hanada, T. Mori, Y. Tsukahara, M. Hashiguchi, H. Ogata

Research output: Contribution to journalArticle

10 Citations (Scopus)

Abstract

We have estimated the pharmacokinetic and pharmacodynamic interactions of verapamil (VP) enantiomers and also the interaction between VP and its metabolite, norverapamil (NVP). ECGs of conscious rabbits were studied to determine the pharmacokinetics of VP enantiomers and racemic NVP in relation to their prolongation effect on PR intervals, which were used as an index of VP's antiarrhythmic effect. Plasma free fractions of VP enantiomers showed constant values at concentrations ranging from 0.022 to 1.10 μM. There were no interactions between enantiomers or between VP and NVP. The pharmacological effect of the S-enantiomer (S-VP), which was determined by linear regression analysis, showed it was about 20 times more potent than that of the R-enantiomer (R-VP). The effect of racemic VP was the simple sum of those elicited by both enantiomers. These relationships were not significantly different between intravenous infusion and bolus injection. Simultaneous intravenous infusion of NVP had no influence on the PR intervals. In conclusion, we demonstrated that the relationship between plasma unbound concentration of VP enantiomers and their pharmacological effect was the simple sum of two enantiomers.

Original languageEnglish
Pages (from-to)806-810
Number of pages5
JournalBiological and Pharmaceutical Bulletin
Volume24
Issue number7
DOIs
Publication statusPublished - 2001 Jul 24
Externally publishedYes

Keywords

  • Enantiomer
  • Interaction
  • Norverapamil
  • Pharmacodynamics
  • Rabbit
  • Verapamil

ASJC Scopus subject areas

  • Pharmacology
  • Pharmaceutical Science

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