Pharmacokinetics of (+)-, (-)- and (+/-)-verapamil after intravenous administration.
The pharmacokinetics of (+)-, (-)-, and (+/-)-verapamil were studied in five healthy volunteers following i.v. administration of the drugs. Pronounced differences of the various pharmacokinetic parameters were observed between the (-)- and (+)-isomers. The values for CL, V, Vz, and Vss of the (-)-isomer were substantially higher as compared to the (+)-isomer, whereas terminal t 1/ 2Z was nearly identical for both isomers. No dose dependency of the pharmacokinetics could be observed in two subjects who received 5, 7.5 and 10 mg of (-)- and 5, 25 and 50 mg of (+)-verapamil. Protein binding for the two isomers was also different. The fu of (-)- (0.11) was almost twice as much as that of (+)-verapamil (0.064). Pharmacokinetic parameters of (+/-)-verapamil, which was administered to three subjects who had received (+)- and (-)-verapamil, were very similar to the averaged values of the isomers given separately. Due to the higher CL of (-)-verapamil the extraction ratio of the (-)-isomer is substantially higher. Thus, it can be anticipated that following oral administration of racemic verapamil bioavailability of (-)-verapamil will be substantially less. Since the (-)-isomer is more potent than the (+)-isomer, the present findings could explain the reported differences in the concentration-effect relationship after i.v. and oral administration of racemic verapamil.
D000328:Adult; D001682:Biological Availability; D001798:Blood Proteins / Q000378:metabolism; D008401:Gas Chromatography-Mass Spectrometry; D006207:Half-Life; D006801:Humans; D007263:Infusions, Parenteral; D007700:Kinetics; D008297:Male; D011485:Protein Binding; D013237:Stereoisomerism; D014700:Verapamil / Q000008:administration & dosage / Q000378:metabolism*
D001798:Blood Proteins; D014700:Verapamil