Pharmacokinetics and Comparative Bioavailability Study of Two Clarithromycin Suspensions Following Administration of a Single Oral Dose to Healthy Volunteers

Abstract

The aim of the present study was to compare the pharmacokinetics and bioavailability of two commercial brands of clarithromycin (CAS 81103-11-9) suspensions in healthy male Iranian volunteers. In an open label, single-dose, randomized study with a crossover design an equivalent 500-mg clarithromycin suspension was given orally to each of 24 subjects as a single dose on two treatment days. The treatment periods were separated by a one-week washout period. Blood samples were drawn at different time points and the separated plasma was kept frozen at -20 degrees C for subsequent analysis. The plasma concentrations of the drug were analyzed by a rapid and sensitive HPLC method with UV detection. Mean maximum serum concentrations of 2256.5 +/- 590.1 ng/mL and 2840.2 +/- 717.5 ng/mL were obtained for the test and reference formulation, respectively. The AUC(0-infinity) of clarithromycin was on average 45008.7 +/- 10989.9 ng . h/mL for the test and 45221.3 +/- 2155.7 ng . h/mL for the reference formulation. The calculated 90% confidence intervals for the ratio of C(max) (81.98-94.26%), AUC(0)(t) (91.6-109.15%) and AUC(0)(infinity) (93.08-110.85%) values for the test and reference products were all within the 85-120% interval proposed by the FDA and EMEA. Therefore the clarithromycin suspension of the test and reference formulations are bioequivalent in terms of rate and extent of absorption.