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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.
Neely, Michael; Kaplan, Edward L; Blumer, Jeffrey L; Faix, Dennis J; Broderick, Michael P.
Afiliación
  • Neely M; Laboratory of Applied Pharmacokinetics and Bioinformatics, Children's Hospital of Los Angeles, and Keck School of Medicine of USC, Los Angeles, California, USA mneely@usc.edu.
  • Kaplan EL; Department of Pediatrics, University of Minnesota Medical School, Minneapolis, Minnesota, USA.
  • Blumer JL; Departments of Pediatrics and Pharmacology, Case Western Reserve University School of Medicine, Cleveland, Ohio, USA.
  • Faix DJ; Operational Infectious Diseases Department, Naval Health Research Center, San Diego, California, USA.
  • Broderick MP; Operational Infectious Diseases Department, Naval Health Research Center, San Diego, California, USA.
Antimicrob Agents Chemother ; 58(11): 6735-41, 2014 Nov.
Article en En | MEDLINE | ID: mdl-25182635
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.
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Penicilina G Benzatina / Streptococcus pyogenes / Antibacterianos Tipo de estudio: Prognostic_studies / Risk_factors_studies Límite: Adolescent / Adult / Humans / Male Idioma: En Revista: Antimicrob Agents Chemother Año: 2014 Tipo del documento: Article País de afiliación: Estados Unidos Pais de publicación: Estados Unidos
Texto completo
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Penicilina G Benzatina / Streptococcus pyogenes / Antibacterianos Tipo de estudio: Prognostic_studies / Risk_factors_studies Límite: Adolescent / Adult / Humans / Male Idioma: En Revista: Antimicrob Agents Chemother Año: 2014 Tipo del documento: Article País de afiliación: Estados Unidos Pais de publicación: Estados Unidos