Premium
Influence of metabolites on protein binding of verapamil enantiomers.
Author(s) -
Johnson JA,
Akers WS
Publication year - 1995
Publication title -
british journal of clinical pharmacology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.216
H-Index - 146
eISSN - 1365-2125
pISSN - 0306-5251
DOI - 10.1111/j.1365-2125.1995.tb04492.x
Subject(s) - verapamil , pharmacology , chemistry , free fraction , plasma protein binding , medicine , calcium , organic chemistry
This study investigated the effect of verapamil metabolites on R‐ and S‐ verapamil protein binding in plasma samples collected from subjects prior to rac‐verapamil dosing and following single dose and steady state rac‐verapamil dosing. In vitro studies of the effects of norverapamil, D617 and D620 on R‐ and S‐verapamil protein binding were also performed. Protein binding of R‐ and S‐verapamil was unchanged following single and multiple doses of rac‐verapamil as compared with protein binding in pre‐dose samples. In vitro, norverapamil had no effect on R‐ and S‐verapamil protein binding up to 1000 ng ml‐1. Norverapamil 5000 ng ml‐1 caused a 30% increase in free fraction of both R‐ and S‐verapamil. D617 and D620 concentrations up to 5000 ng ml‐ 1 had no effect on R‐ and S‐verapamil protein binding. We conclude the metabolites of verapamil have no clinically significant effect on R‐ and S‐verapamil protein binding.