Stereoselective pharmacokinetics and pharmacodynamics of disopyramide and its metabolite in rabbits

M. Horikawa, M. Yasumuro, M. Kanno, K. Hanada, Masayuki Hashiguchi, H. Ogata

Research output: Contribution to journalArticle

Abstract

The extent to which interactions between enantiomers of disopyramide and between disopyramide and its metabolite, mono-N-dealkylated disopyramide (MND), contribute to stereoselectivity of the anti-arrhythmic effect has been investigated in rabbits by measuring the prolongation of the QUc interval. The plasma unbound fraction of disopyramide enantiomers was constant at a concentration range of 1.44-28.9 μM. An intravenous infusion study of the disopyramide enantiomer or racemate suggested that the S-enantiomer had a pharmacological effect, determined by linear regression analysis, approximately 3.3-times more potent than that of the R-enantiomer. Furthermore, the effect caused by racemic disopyramide was that sum of the elicited by both enantiomers individually. No significant difference was observed between the slope of linear regression analysis of intravenous infusion and that of intravenous bolus injection. Single intravenous bolus injection of MND did not affect the QUc intervals. In conclusion, the S-enantiomer of disopyramide was approximately 3.3-times more potent pharmacologically than the R-enantiomer. The relationship between plasma concentration of the disopyramide enantiomers and pharmacological effect was the sum of each enantiomer individually.

Original languageEnglish
Pages (from-to)1621-1628
Number of pages8
JournalJournal of Pharmacy and Pharmacology
Volume53
Issue number12
DOIs
Publication statusPublished - 2001
Externally publishedYes

Fingerprint

Disopyramide
Pharmacokinetics
Rabbits
Intravenous Infusions
Intravenous Injections
Linear Models
Regression Analysis
Pharmacology
Anti-Arrhythmia Agents

ASJC Scopus subject areas

  • Pharmacology
  • Pharmaceutical Science

Cite this

Stereoselective pharmacokinetics and pharmacodynamics of disopyramide and its metabolite in rabbits. / Horikawa, M.; Yasumuro, M.; Kanno, M.; Hanada, K.; Hashiguchi, Masayuki; Ogata, H.

In: Journal of Pharmacy and Pharmacology, Vol. 53, No. 12, 2001, p. 1621-1628.

Research output: Contribution to journalArticle

Horikawa, M. ; Yasumuro, M. ; Kanno, M. ; Hanada, K. ; Hashiguchi, Masayuki ; Ogata, H. / Stereoselective pharmacokinetics and pharmacodynamics of disopyramide and its metabolite in rabbits. In: Journal of Pharmacy and Pharmacology. 2001 ; Vol. 53, No. 12. pp. 1621-1628.
@article{5ab6a6e9b4904366b90612c7baed69e0,
title = "Stereoselective pharmacokinetics and pharmacodynamics of disopyramide and its metabolite in rabbits",
abstract = "The extent to which interactions between enantiomers of disopyramide and between disopyramide and its metabolite, mono-N-dealkylated disopyramide (MND), contribute to stereoselectivity of the anti-arrhythmic effect has been investigated in rabbits by measuring the prolongation of the QUc interval. The plasma unbound fraction of disopyramide enantiomers was constant at a concentration range of 1.44-28.9 μM. An intravenous infusion study of the disopyramide enantiomer or racemate suggested that the S-enantiomer had a pharmacological effect, determined by linear regression analysis, approximately 3.3-times more potent than that of the R-enantiomer. Furthermore, the effect caused by racemic disopyramide was that sum of the elicited by both enantiomers individually. No significant difference was observed between the slope of linear regression analysis of intravenous infusion and that of intravenous bolus injection. Single intravenous bolus injection of MND did not affect the QUc intervals. In conclusion, the S-enantiomer of disopyramide was approximately 3.3-times more potent pharmacologically than the R-enantiomer. The relationship between plasma concentration of the disopyramide enantiomers and pharmacological effect was the sum of each enantiomer individually.",
author = "M. Horikawa and M. Yasumuro and M. Kanno and K. Hanada and Masayuki Hashiguchi and H. Ogata",
year = "2001",
doi = "10.1211/0022357011778223",
language = "English",
volume = "53",
pages = "1621--1628",
journal = "Journal of Pharmacy and Pharmacology",
issn = "0022-3573",
publisher = "Pharmaceutical Press",
number = "12",

}

TY - JOUR

T1 - Stereoselective pharmacokinetics and pharmacodynamics of disopyramide and its metabolite in rabbits

AU - Horikawa, M.

AU - Yasumuro, M.

AU - Kanno, M.

AU - Hanada, K.

AU - Hashiguchi, Masayuki

AU - Ogata, H.

PY - 2001

Y1 - 2001

N2 - The extent to which interactions between enantiomers of disopyramide and between disopyramide and its metabolite, mono-N-dealkylated disopyramide (MND), contribute to stereoselectivity of the anti-arrhythmic effect has been investigated in rabbits by measuring the prolongation of the QUc interval. The plasma unbound fraction of disopyramide enantiomers was constant at a concentration range of 1.44-28.9 μM. An intravenous infusion study of the disopyramide enantiomer or racemate suggested that the S-enantiomer had a pharmacological effect, determined by linear regression analysis, approximately 3.3-times more potent than that of the R-enantiomer. Furthermore, the effect caused by racemic disopyramide was that sum of the elicited by both enantiomers individually. No significant difference was observed between the slope of linear regression analysis of intravenous infusion and that of intravenous bolus injection. Single intravenous bolus injection of MND did not affect the QUc intervals. In conclusion, the S-enantiomer of disopyramide was approximately 3.3-times more potent pharmacologically than the R-enantiomer. The relationship between plasma concentration of the disopyramide enantiomers and pharmacological effect was the sum of each enantiomer individually.

AB - The extent to which interactions between enantiomers of disopyramide and between disopyramide and its metabolite, mono-N-dealkylated disopyramide (MND), contribute to stereoselectivity of the anti-arrhythmic effect has been investigated in rabbits by measuring the prolongation of the QUc interval. The plasma unbound fraction of disopyramide enantiomers was constant at a concentration range of 1.44-28.9 μM. An intravenous infusion study of the disopyramide enantiomer or racemate suggested that the S-enantiomer had a pharmacological effect, determined by linear regression analysis, approximately 3.3-times more potent than that of the R-enantiomer. Furthermore, the effect caused by racemic disopyramide was that sum of the elicited by both enantiomers individually. No significant difference was observed between the slope of linear regression analysis of intravenous infusion and that of intravenous bolus injection. Single intravenous bolus injection of MND did not affect the QUc intervals. In conclusion, the S-enantiomer of disopyramide was approximately 3.3-times more potent pharmacologically than the R-enantiomer. The relationship between plasma concentration of the disopyramide enantiomers and pharmacological effect was the sum of each enantiomer individually.

UR - http://www.scopus.com/inward/record.url?scp=0035679755&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=0035679755&partnerID=8YFLogxK

U2 - 10.1211/0022357011778223

DO - 10.1211/0022357011778223

M3 - Article

C2 - 11804392

AN - SCOPUS:0035679755

VL - 53

SP - 1621

EP - 1628

JO - Journal of Pharmacy and Pharmacology

JF - Journal of Pharmacy and Pharmacology

SN - 0022-3573

IS - 12

ER -