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Myocardial uptake kinetics of tocainide enantiomers in the isolated perfused rabbit heart
Author(s) -
Christensen Ellen Bech,
Hansen Steen Honoré,
Rasmussen Søren Nørgaard
Publication year - 1995
Publication title -
chirality
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.43
H-Index - 77
eISSN - 1520-636X
pISSN - 0899-0042
DOI - 10.1002/chir.530070310
Subject(s) - chemistry , enantiomer , perfusion , stereoselectivity , kinetics , distribution (mathematics) , chromatography , pharmacology , stereochemistry , medicine , biochemistry , mathematical analysis , physics , mathematics , quantum mechanics , catalysis
Abstract The extent of myocardial accumulation of tocainide, administered as single enantiomers and as well as racemate, was determined in the isolated, spontaneous beating rabbit heart. The heart was retrogradely perfused at a constant rate and fractions of the perfusate were collected during and after infusion. Kinetic parameters for myocardial accumulation and disposition of tocainide were indirectly determined from drug concentration/time course in the outflow perfusate. No stereoselectivity in myocardial accumulation was observed. A two compartment model with mean half‐lives for distribution and elimination of 0.60 and 3.78 min, respectively, was fitted to the accumulation and disposition data. At steady‐state, tocainide enantiomers were accumulated about three times in the myocardium relative to the perfusion liquid. © 1995 Wiley‐Liss, Inc.