Validation of the hepatic blood flow rate model for verapamil first-pass metabolism.
The bioavailability of a new retard tablet formulation of verapamil was investigated in a randomized cross-over bioequivalence study on 12 healthy subjects. The drug was given in the form of a single 240-mg oral dose of a new retard tablet formulation, or as a standard retard tablet at the same dose to all subjects, followed by a single intravenous (i.v.) dose of 5 mg to 8 of the 12 subjects. Plasma verapamil concentrations were determined by a high performance liquid chromatography (HPLC) method. The bioavailability of the new peroral retard formulation was (20.00 +/- 4.30)% and was in reasonable agreement with that determined for the already registered verapamil retard formulation, i.e. (19.46 +/- 4.02)%, thereby indicating bioequivalence. For the prediction of systemic availability and estimation of the first-pass metabolism, only based on the data for peroral plasma levels, a hepatic blood flow rate limited model was used. In our experience, this model has been found to be extremely useful in providing reasonable estimates of verapamil first-pass effect.
Popović
Jovan
J
Department of Pharmacology, Toxicology and Clinical Pharmacology, Faculty of Medicine, Novi Sad, Republic of Serbia.
D000284:Administration, Oral; D000328:Adult; D001682:Biological Availability; D001783:Blood Flow Velocity; D002121:Calcium Channel Blockers / Q000008:administration & dosage / Q000097:blood / Q000493:pharmacokinetics*; D002851:Chromatography, High Pressure Liquid; D018592:Cross-Over Studies; D003692:Delayed-Action Preparations; D005260:Female; D006801:Humans; D007275:Injections, Intravenous; D008102:Liver Circulation; D008297:Male; D008875:Middle Aged; D008954:Models, Biological; D011237:Predictive Value of Tests; D012016:Reference Values; D015203:Reproducibility of Results; D013810:Therapeutic Equivalency; D014700:Verapamil / Q000008:administration & dosage / Q000097:blood / Q000493:pharmacokinetics*
D002121:Calcium Channel Blockers; D003692:Delayed-Action Preparations; D014700:Verapamil