Pharmacokinetics and Safety of Intramuscular Injectable Benzathine Penicillin G in Japanese Healthy Participants

Abstract

AbstractAn intramuscular (IM) suspension of benzathine penicillin G (BPG) has been used as first‐line therapy for the treatment of syphilis worldwide since its approval in the 1950s. However, there are limited reports about the pharmacokinetics of BPG. A Phase 1 study was conducted on eight Japanese healthy participants to investigate the pharmacokinetics (samples collected predose to 648 h post‐dose) and safety of 2.4 million units of BPG after a single IM injection. Following administration, penicillin G, the active moiety of BPG, was absorbed slowly from the injection site with a median time to Cmax (tmax) of 48 h post‐dose. After the achievement of Cmax, concentrations of penicillin G declined slowly in a monophasic fashion with a mean apparent terminal half‐life of 189 h. Geometric mean AUCinf and Cmax were 50770 ng•h/mL and 259 ng/mL, respectively. Median time (range) above the well‐accepted therapeutic concentration (18 ng/mL) for syphilis treatment was 561 h (439–608 h [18–25 days]), which reached and exceeded the necessary duration of 7–10 days for syphilis treatment. Two participants were underdosed with residual drug left in the syringe due to the high viscosity of the drug product. Only one (12.5%) participant reported a mild adverse event of nasopharyngitis, which was considered not related to the study treatment. The study results supported BPG approval in Japan as an option for syphilis treatment.