Bioequivalence Evaluation of Two Different Tablet Formulations of Tinidazole in Healthy Volunteers

Abstract

The bioequivalence of two different tablet formulations of tinidazole (CAS 19387-91-8) was determined in healthy volunteers after a single dose in a randomized crossover study, with a 1-week washout period between the doses. Reference and test products were administered to 24 volunteers with 240 mL water after overnight fasting. Plasma concentrations of tinidazole were monitored by a high-performance liquid chromatographic method (HPLC) over a period of 72 h after the administration. The pharmacokinetic parameters AUC_0–t, AUC_0–∞, C_max, T_max, T_(1/2)el and β were determined from plasma concentration time profile of both formulations and found to be in good agreement with previously reported values. The calculated pharmacokinetic parameters were compared statistically to evaluate bioequivalence between the two brands. The analysis of variance (ANOVA) did not show any significant difference between the two formulations and 90% confidence intervals for the ratio of C_max (93.9 – 102.6%), AUC_0–t (94.9–101.1%) and AUC_0–∞ (94.6-100.8%) values for the test and reference products were within the 80 – 125% interval, satisfying the bioequivalence criteria of the European Committee for Proprietary Medicinal Products and the US Food and Drug Administration Guidelines. These results indicate that the test and the reference products of tinidazole are bioequivalent and, thus, may be prescribed interchangeably.

Key words

Antimicrobials - CAS 19387-91-8 - Tinidazole, bioequivalence, pharmacokinetics

• Literature

• 1 Lamp KC, Freeman CD, Klutman NE, Lacy MK. Pharmacokinetics and pharmacodynamics of the nitroimidazole antimicrobials. Clin Pharmacokinet. 1999; 36: 353-373
• 2 Chaikin P, Alton KB, Sampson C, Weintraub HS. Pharmacokinetics of tinidazole in male and female subjects. J Clin Pharmacol. 1982; 22: 562-570
• 3 Chow SC, Liu JP. Design and Analysis of Bioavailability and Bioequivalence Studies. 2nd ed. New York:: Marcel Dekker; 2000
• 4 Chen ML, Shah V, Patnaik R, Adams W, Hussain A, Conner D. et al Bioavailability and bioequivalence: an FDA regulatory overview. Pharm Res. 2001; 18: 1645-1650
• 5 Bressole F, Bromet-Petit M, Audran M. Validation of liquid chromatographic and gas chromatographic methods. Applications to pharmacokinetics. J Chromatogr B Biomed Sci Appl. 1996; 686: 3-10
• 6 Causon R.. Validation of chromatographic methods in biomedical analysis: viewpoint and discussion. J Chromatogr B Biomed Sci Appl. 1997; 689: 175-80
• 7 U.S. Food and Drug Administration, Center for Drug Evaluation and Research. Guidance for Industry: Bioanalytical Method Validation. Rockville, MD: Division of Bioequivalence. Office of Generic Drugs; 2001.
• 8 Ritschel WA. Handbook of Basic Pharmacokinetics. 4th ed. Hamilton: Drug Intelligence; 1992
• 9 European Agency for the Evaluation of Medicinal Products. Human Medicines Evaluation Unit. Committee for Proprietary Meidicinal Products. Note for guidance on the investigation of bioavailability and bioequivalence. London: EMEA; 1998.
• 10 US Food and Drug Administration, Title 21 Code of Federal Regulations (CFR) Part 320, Office of federal Register, National Archives and Records Administration; 2001.
• 11 Rajnarayana K, Chaluvadi MR, Alapati VR, Mada SR, Jayasagar G, Krishna DR. Validated HPLC method for the determination of tinidazole in human serum and its application in clinical pharmacokinetic study. Pharmazie. 2002; 57: 535-7