A population pharmacokinetic modeling approach shows that serum penicillin G concentrations are below inhibitory concentrations by two weeks after benzathine penicillin G injection in the majority of young adults

• Published in: Antimicrobial agents and chemotherapy Vol. 58; no. 11; pp. 6735 - 6741
• Main Authors: Neely, Michael, Kaplan, Edward L, Blumer, Jeffrey L, Faix, Dennis J, Broderick, Michael P
• Format: Journal Article
• Language: English
• Published: United States American Society for Microbiology 01.11.2014
• Subjects: Adolescent; Adult; Anti-Bacterial Agents; Anti-Bacterial Agents - blood; Anti-Bacterial Agents - metabolism; Anti-Bacterial Agents - pharmacokinetics; Humans; Male; Microbial Sensitivity Tests; Penicillin G Benzathine; Penicillin G Benzathine - blood; Penicillin G Benzathine - metabolism; Penicillin G Benzathine - pharmacokinetics; Pharmacology; Respiratory Tract Infections - drug therapy; Respiratory Tract Infections - microbiology; Rheumatic Heart Disease - microbiology; Rheumatic Heart Disease - prevention & control; Streptococcus pyogenes; Streptococcus pyogenes - drug effects; Syphilis - drug therapy; Syphilis - microbiology; Young Adult
• ISSN: 0066-4804; 1098-6596
• DOI: 10.1128/AAC.02744-14

Serum penicillin G falls to low levels 2 weeks after injection as benzathine penicillin G (BPG) in young adults. Using Pmetrics and previously reported penicillin G pharmacokinetic data after 1.2 million units were given as BPG to 329 male military recruits, here we develop the first reported population pharmacokinetic model of penicillin G after BPG injection. We simulated time-concentration profiles over a broad range of pediatric and adult weights after alternative doses and dose frequencies to predict the probability of maintaining serum penicillin G concentrations of >0.02 mg/liter, a proposed protective threshold against group A Streptococcus pyogenes (GAS). The final population model included linear absorption into a central compartment, distribution to and from a peripheral compartment, and linear elimination from the central compartment, with allometrically scaled volumes and rate constants. With 1.2 million units of BPG given intramuscularly every 4 weeks in four total doses, only 23.2% of 5,000 simulated patients maintained serum penicillin G trough concentrations of >0.02 mg/liter 4 weeks after the last dose. When the doses were 1.8 million units and 2.4 million units, the percentages were 30.2% and 40.7%, respectively. With repeated dosing of 1.2 million units every 3 weeks and every 2 weeks for 4 doses, the percentages of simulated patients with a penicillin G trough concentration of >0.02 mg/liter were 37.8% and 65.2%, respectively. Our simulations support recommendations for more frequent rather than higher BPG doses to prevent recurrent rheumatic heart disease in areas of high GAS prevalence or during outbreaks.