title: Influence of metabolites on protein binding of verapamil enantiomers.
abstract: 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.
authors.affiliation: Department of Clinical Pharmacy, College of Pharmacy, University of Tennessee, Memphis 38163, USA.
authors.forename: J A
authors.initials: JA
authors.lastname: Johnson
authors.forename: W S
authors.initials: WS
authors.lastname: Akers
mesh_terms: D000704:Analysis of Variance; D001682:Biological Availability; D001798:Blood Proteins / Q000378:metabolism*; D002851:Chromatography, High Pressure Liquid; D003692:Delayed-Action Preparations; D006801:Humans; D066298:In Vitro Techniques; D008297:Male; D009570:Nitriles; D011485:Protein Binding / Q000187:drug effects; D013237:Stereoisomerism; D014700:Verapamil / Q000008:administration & dosage / Q000031:analogs & derivatives / Q000097:blood / Q000737:chemistry / Q000378:metabolism* / Q000494:pharmacology
chemical_list: D001798:Blood Proteins; D003692:Delayed-Action Preparations; D009570:Nitriles; C016906:alpha-(3-aminopropyl)-3,4-dimethoxy-alpha-(1-methylethyl)benzeneacetonitrile; C482241:2-(3,4-dimethoxyphenyl)-5-amino-2-isopropylvaleronitrile; C016904:norverapamil; D014700:Verapamil