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 °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 2 256.5 ± 590.1 ng/mL and 2 840.2 ± 717.5 ng/mL were obtained for the test and reference formulation, respectively. The AUC_0–infinity of clarithromycin was on average 45 008.7 ± 10 989.9 ng · h/mL for the test and 45 221.3 ± 2155.7 ng h/mL for the reference formulation. The calculated 90% confidence intervals for the ratio of C_max (81.98–94.26%), (91.6–109.15%) and (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.

Key words

CAS 81103-11-9 - Clarithromycin, bioavailability, bioequivalence, pharmacokinetics - Klarexir® - Macrolide antibiotic

• References

• 1 Guay DR, Gustavson LE, Devcich KJ, Zhang J, Cao G, Olson CA. Pharmacokinetics and tolerability of extended-release clarithromycin. Clin Ther. 2001; 23 (4) 566-77
• 2 Nash KA. Intrinsic macrolide resistance in Mycobacterium smegmatis is conferred by a novel erm gene, erm(38). Anti-microb Agents Chemother. 2003; 47 (10) 3053-60
• 3 Andini N, Nash KA. Intrinsic macrolide resistance of the Mycobacterium tuberculosis complex is inducible. Antimi-crob Agents Chemother. 2006; 50 (7) 2560-2
• 4 Brown BA, Wallace Jr RJ. Onyi GO. Activities of clarithromycin against eight slowly growing species of nontuberculous mycobacteria, determined by using a broth microdilution MIC system. Antimicrob Agents Chemother. 1992; 36 (9) 1987-90
• 5 Fernandes PB, Hardy DJ, McDaniel D, Hanson CW, Swan-son RN. In vitro and in vivo activities of clarithromycin against Mycobacterium avium. Antimicrob Agents Chemother. 1989; 33 (9) 1531-4
• 6 Mor N, Esfandiari A. Synergistic activities of clarithromycin and pyrazinamide against Mycobacterium tuberculosis in human macrophages. Antimicrob Agents Chemother. 1997; 41 (9) 2035-6
• 7 Sweetman SC. Martindale The complete Drug Reference. London: The Pharmaceutical Press; 2007.
• 8 Ferrero JL, Bopp BA, Marsh KC, Quigley SC, Johnson MJ, Anderson DJ, Lamm JE, Tolman KG, Sanders SW, Cava-naugh JH et al Metabolism and disposition of clarithromycin in man. Drug Metab Dispos. 1990; 18 (4) 441-6
• 9 Guay DR, Craft JC. Overview of the pharmacology of clarithromycin suspension in children and a comparison with that in adults. Pediatr Infect Dis J. 1993; 12 (12 Suppl 3) S106-11
• 10 Amini H, Ahmadiani A. Sensitive determination of clarithromycin in human plasma by high-performance liquid chromatography with spectrophotometric detection. J Chromatogr B Analyt Technol Biomed Life Sci. 2005; 817 (2) 193-7
• 11 Zakeri-Milani P, Valizadeh H, Islambulchilar Z. Comparative bioavailability study of two cefixime formulations administered orally in healthy male volunteers. Arzneimittelforschung. 2008; 58 (2) 97-100
• 12 Guidance for industry, bioavailability and bioequivalence studies for orally administered drug products; General considerations. US Department of Health and Human Services, Food and Drug Administration, Center for Drug Evaluation and Reserch (CDER), July 2002 BP.