Development of reduced-size telithromycin tablet -Results of a bioequivalence study comparing reduced-size and currently available formulations-

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Vol.53 No.4 April 2005

Roza Ishihara¹⁾, Koichi Enomoto²⁾, Kenichi Abe³⁾, Montay Guy⁴⁾ and Shigeru Yakou⁵⁾

¹⁾Clinical Discovery &, Human Pharmacology, Lead Optimization,
²⁾Analytical Sciences, Product Realization Operations Center,
³⁾Pharmaceutical Sciences, Product Realization Operations Center, Drug Innovation &, Approval Division, Aventis Pharma Japan, Tokyo Opera City Tower, 3-20-2 Nishi Shinjuku, Shinjuku-ku, Tokyo, Japan
⁴⁾Clinical Pharmacokinetics, Drug Metabolism and Pharmacokinetics, Aventis Pharma France
⁵⁾Tokyo Women's Medical University Daini Hospital

Abstract

Telithromycin (TEL), an oral ketolide antibiotic, is currently available as a 300 mg tablet. To facilitate admin-istration, a reduced-size tablet, about 75% of the currently available formulation in volume, was developed. As part of this development, we conducted dissolution and bioequivalence studies in human subjects to evaluate formulation bioequivalence. In the dissolution study, an average exceeding 85% of both currently available and reduced-size tablets dissolved in all test solutions within 15 minutes. Since results met criteria in bioequivalence study guidelines, dissolution profiles for both formulations were determined to be equivalent. In the bioequivalence study where a single dose of 600 mg was administered to 36 male and female subjects, mean ratios between reduced-size and currently available tablets for the maximum plasma concentration (C_max) was 94.2% and the area-under-plasma-concentration-time curve (AUC_0-Z) was 97.0%. The two-sided 90% confidence interval was 80-125%, within the bioequivalence acceptance limit. The two formulations were therefore determined to be equivalent.
Overall results thus indicate that TEL reduced-size and currently available tablet formulations were biologically equivalent.

Key word

telithromycin, reduced-size formulation, dissolubility, bioequivalence, ketolide

Received

December 27, 2004

Accepted

March 18, 2005

Jpn. J. Chemother. 53 (4): 268-273, 2005