title: Population pharmacokinetic analysis and dosing regimen optimization of penicillin G in patients with infective endocarditis.
abstract: BACKGROUND
  This study was designed to evaluate the population pharmacokinetics (popPK) of penicillin G in patients with infective endocarditis and establish a dosage regimen based on pharmacokinetic data and clinical outcome.
  
  
  METHODS
  Forty-six serum penicillin G samples from 25 individuals were analyzed using a nonlinear mixed-effects model. popPK were estimated using a one-compartment model. We created a receiver operating characteristic (ROC) curve for penicillin G efficacy and the ratio of its minimum concentration (Cmin)/minimum inhibitory concentration (MIC). Simulations were used to optimize the penicillin G dosage regimen using this ratio.
  
  
  RESULTS
  Estimated popPK were: CL (L/h) = 0.21 × creatinine clearance (CLcr) (mL/min), Vd (L) = 28.9. The areas under the ROC curves were 0.87 for clinical efficacy. The cut-off value of penicillin G Cmin/MIC was 60. The continuous administration of 1 million IU penicillin G/h was necessary to achieve a positive outcome for patients with normal renal function (CLcr ≥ 60 mL/min).
  
  
  CONCLUSIONS
  Our findings suggest that population-based parameters are useful for evaluating penicillin G pharmacokinetics and that an individualized dosage should be determined based on a described dosage regimen.
authors.affiliation: Department of Pharmacy, Kitasato University Hospital, 1-15-1 Kitasato, Minami-Ku, Sagamihara, Kanagawa 252-0375 Japan.
authors.forename: Toshiaki
authors.initials: T
authors.lastname: Komatsu
authors.affiliation: Department of Cardiovascular Medicine, Kitasato University School of Medicine, Sagamihara, Japan.
authors.forename: Takayuki
authors.initials: T
authors.lastname: Inomata
authors.affiliation: Department of Cardiovascular Medicine, Kitasato University School of Medicine, Sagamihara, Japan.
authors.forename: Ichiro
authors.initials: I
authors.lastname: Watanabe
authors.affiliation: Department of Pharmacy, Kitasato University Hospital, 1-15-1 Kitasato, Minami-Ku, Sagamihara, Kanagawa 252-0375 Japan.
authors.forename: Masahiro
authors.initials: M
authors.lastname: Kobayashi
authors.affiliation: Department of Pharmacy, Kitasato University Hospital, 1-15-1 Kitasato, Minami-Ku, Sagamihara, Kanagawa 252-0375 Japan.
authors.forename: Hideya
authors.initials: H
authors.lastname: Kokubun
authors.affiliation: Department of Cardiovascular Medicine, Kitasato University School of Medicine, Sagamihara, Japan.
authors.forename: Junya
authors.initials: J
authors.lastname: Ako
authors.affiliation: Department of Pharmacy, Kitasato University Hospital, 1-15-1 Kitasato, Minami-Ku, Sagamihara, Kanagawa 252-0375 Japan.
authors.forename: Koichiro
authors.initials: K
authors.lastname: Atsuda
keywords: Dosing optimization; Nonlinear mixed-effects model; Penicillin G; Population pharmacokinetics