Population pharmacokinetics of penicillin G: insights into increased clearance at low concentrations to guide development of improved long-acting formulations for syphilis

Citation:
Yoo O, Salman S, Hla TK, Osowicki J, Page-Sharp M, Marsh JA, Barr R, Azzopardi K, Morici M, Batty KT, Enkel SL, Kado J, Hatchuel L, Fulurija A, McCarthy JS, Snelling T, Steer AC, Carapetis J, Manning L. Population pharmacokinetics of penicillin G: insights into increased clearance at low concentrations to guide development of improved long-acting formulations for syphilis and prevention of rheumatic fever. Antimicrob Agents Chemother. 2025;69(7):e0026925.

Keywords:
benzathine penicillin G; benzylpenicillin; cystatin C; eGFR; penicillin G; pharmacokinetics; population PK modeling; renal clearance; rheumatic fever; rheumatic heart disease; syphilis

Abstract:
Although benzylpenicillin (penicillin G) is listed by the World Health Organization as an Essential Medicine, dose optimization is a persistent challenge, especially for long-acting intramuscular formulations. Maintaining sustained antibiotic exposure at target concentrations is crucial for secondary chemoprophylaxis of rheumatic heart disease and treatment of syphilis.