Bioavailability comparison study of two benzathine benzylpenicillin 1,200,000 IU intramuscular formulations in healthy male participants under fast state

Abstract

Introduction: Benzathine benzylpenicillin G is a drug present in the list of essential medicines of the World Health Organization and largely used in Brazil, where this antibiotic is used for treating pneumonias, pharyngitis, syphilis, and other infections caused by Gram-positive bacteria, being one of the most prescribed antibiotics of the public healthcare system. Objective: The objective of this study was to evaluate the relative bioavailability of two formulations of benzathine benzylpenicillin (Benzetacil®) 1,200,000 IU, both manufactured by Eurofarma Laboratórios S/A, by comparison of plasma levels of both drugs administered intramuscularly, evaluating the pharmacokinetic parameters: Cmax and AUC0-t, being t=672 h. Methods: A randomized, parallel, open-label study with one treatment and one period in 168 healthy male volunteers. Subjects received the test or reference formulations by intramuscular injection. A total of 20 blood samples were collected after administration for plasmatic quantification of the drug by LC-MS/MS along 672 h. Results: Both formulations were considered well tolerated, and no serious adverse event was reported during the trial. Cmax and AUC0-t were compared: the rate between test and reference formulations for Cmax was 97.75% with confidence interval (CI) (86.34–110.67%) and power 90.55%. The rate between test and reference formulations for AUC0-t was 91.15% CI (85.29–97.42%) and power of 99.99%. The rate between test and reference formulations for AUC0-inf was 87.98% with CI (81.29–95.23%) and power of 99.85%. Conclusion: Reference and test formulations were shown to be statistically bioequivalents according to their rate and extension of absorption, based on ANVISA criteria.

Keywords

• Benzathine benzylpenicillin
• Penicillin G
• Bioavailability
• Biological availability
• Pharmacokinetics