Pharmacokinetics and Comparative Bioavailability of Two Diltiazem Tablet Formulations in Healthy Volunteers

Abstract

The pharmacokinetic parameters and bioavailability of diltiazem following a single oral administration of a generic diltiazem 60 mg tablet (Sobhan Pharmaceuticals, Iran) were compared to those of a reference product (Entrydil, Orion Pharmaceuticals, Finland). Twelve healthy male volunteers received a single oral dose of either formulation following overnight fasting in a double blind, randomized, crossover study. Blood samples were collected at selected times during 24 h and diltiazem plasma concentrations were determined with a sensitive HPLC method. Individual pharmacokinetic parameters, t1/2, t1/2(abs), K, Ka, Tmax, Cmax, Vd/F, Cl/F, AUC0-24 and AUC0-∞ were calculated. No significant differences were observed in pharmacokinetic parameters between two formulations. The 90% confidence intervals for the test/reference geometric mean ratios of Cmax, AUC0-24 AUC0-∞ and Cmax/AUC0-∞ were within the conventional bioequivalence range of 0.8 - 1.25.

In-vitro parameters of mean dissolution time (MDT) and time for 70 % dissolution (T70) were also determined. There was a significant difference between the MDT for two dosage forms (p<0.0001). It was concluded that despite of a higher dissolution rate, the test product of diltiazem is bioequivalent to the reference product with respect to the rate and extent of absorption.