Spline functions in convolutional modeling of verapamil bioavailability and bioequivalence. II: Study in healthy volunteers

Abstract

The pharmacokinetics of a new verapamil retard tablet formulation have been investigated in a randomized cross-over bioequivalence study on 12 healthy subjects. The drug was given orally at a single new or standard retard tablet dose of 240mg and at a single intravenous dose of 5mg. Plasma verapamil concentrations were determined by HPLC. New retard tablets produced peak plasma verapamil concentrations of 81.34+/-5.69microg/l, time to peak plasma concentrations of 4.91+/-0.89h and an AUC (0-24h) of 1291+/-103.4h x microg/l, with a terminal phase half-life of 55.1+/-14.9h. After intravenous administration verapamil exhibited biphasic elimination kinetics with a terminal plasma half-life of 2.36+/-0.42h and systemic clearance of 34.32+/-5.81 l/h. Bioavailability of the new peroral retard formulation ranged from 19.49+/-4.41% to 67.69+/-11.70%. Absorption rates and amounts were evaluated by means of the spline-convolutional method. Input rates for the new verapamil retard formulation ranged from 0.77+/-0.20mg/h to 5.57+/-1.58mg/h. The cumulative amount of verapamil input was 39.17+/-9.71% for the new retard tablets. All pharmacokinetic parameters for the new verapamil retard tablet formulation, were in reasonable agreement with the data obtained on already registered verapamil retard formulations, indicating their bioequivalence.

Evaluation of statistical power function for various diclofenac bioequivalence trials with different subject numbers

“…Therefore it is important to predict the time evaluation of the concentration of diclofenac in the blood (17,18). Usuall assumption is that bioequivalent formulations are therapeutically equivalent and exchangeable in clinical practice (19)(20)(21)(22)(23)(24). Once bioequivalence is concluded, in further administration of a bioequvivalent formulation, the time evolu-tion of concentration can be predicted.…”