ENANTIOSELECTIVE DISTRIBUTION OF VERAPAMIL AND NORVERAPAMIL INTO HUMAN AND RAT ERYTHROCYTES - THE ROLE OF PLASMA-PROTEIN BINDING

Citation
Ma. Robinson et R. Mehvar, ENANTIOSELECTIVE DISTRIBUTION OF VERAPAMIL AND NORVERAPAMIL INTO HUMAN AND RAT ERYTHROCYTES - THE ROLE OF PLASMA-PROTEIN BINDING, Biopharmaceutics & drug disposition, 17(7), 1996, pp. 577-587
Citations number
18
Categorie Soggetti
Pharmacology & Pharmacy",Biology
ISSN journal
01422782
Volume
17
Issue
7
Year of publication
1996
Pages
577 - 587
Database
ISI
SICI code
0142-2782(1996)17:7<577:EDOVAN>2.0.ZU;2-T
Abstract
In this in vitro study, the distribution of the enantiomers of verapam il (VER) and its active metabolite, norverapamil (NOR), into the red b lood cells (RBCs) of humans and rats was investigated using a chiral l iquid chromatographic assay. When plasma was replaced with buffer, the distribution of VER and NOR enantiomers into both human and rat RBCs was substantial (RBC:blood concentration ratios, 1.39-1.79), non-stere oselective, concentration (125-1000 ng mL(-1)) linear, and species ind ependent. However, in the presence of plasma, the RBC distribution of VER and NOR was stereoselective, with opposite stereoselectivity for h uman (S > R) and rat (R > S) blood. Additionally, the presence of plas ma caused a reduction in the extent of RBC distribution for both VER a nd NOR enantiomers and in some cases resulted in nonlinearity in the R BC distribution of the enantiomers. Plasma protein binding studies rev ealed opposite stereoselectivity in the free fractions in human (S > R ) and rat (R > S) plasma for both VER and NOR. These data suggest that the stereoselective protein binding is responsible for the apparent s tereoselectivity in the RBC distribution of VER and NOR. The data are also in agreement with the opposite stereoselectivity in the plasma co ncentrations of VER observed in vivo in rats and humans.