Stereoselective pharmacokinetics and pharmacodynamics of verapamil and norverapamil in rabbits

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

研究成果: Article査読

11 被引用数 (Scopus)

抄録

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.

本文言語English
ページ(範囲)806-810
ページ数5
ジャーナルBiological and Pharmaceutical Bulletin
24
7
DOI
出版ステータスPublished - 2001
外部発表はい

ASJC Scopus subject areas

  • 薬理学
  • 薬科学

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