title: Population pharmacokinetics of olprinone in healthy male volunteers.
abstract: BACKGROUND
  Olprinone decreases the cardiac preload and/or afterload because of its vasodilatory effect and increases myocardial contractility by inhibiting phosphodiesterase III.
  
  
  OBJECTIVE
  The objective of this study was to characterize the population pharmacokinetics of olprinone after a single continuous infusion in healthy male volunteers.
  
  
  METHODS
  We used 500 plasma concentration data points collected from nine healthy male volunteers for the study. The population pharmacokinetic analysis was performed using the nonlinear mixed effect model (NONMEM®) software.
  
  
  RESULTS
  The time course of plasma concentration of olprinone was best described using a two-compartment model. The final pharmacokinetic parameters were total clearance (7.37 mL/minute/kg), distribution volume of the central compartment (134 mL/kg), intercompartmental clearance (7.75 mL/minute/kg), and distribution volume of the peripheral compartment (275 mL/kg). The interindividual variability in the total clearance was 12.4%, and the residual error variability (exponential and additive) were 22.2% and 0.129 (standard deviation). The final pharmacokinetic model was assessed using a bootstrap method and visual predictive check.
  
  
  CONCLUSIONS
  We developed a population pharmacokinetic model of olprinone in healthy male adults. The bootstrap method and visual predictive check showed that this model was appropriate. Our results might be used to develop the population pharmacokinetic model in patients.
authors.affiliation: Surgical Operation Department, Asahikawa Medical University Hospital, Hokkaido, Japan.
authors.forename: Takayuki
authors.initials: T
authors.lastname: Kunisawa
authors.affiliation: Clinical Study Management Division, Bell Medical Solutions Inc, Tokyo, Japan.
authors.forename: Hidefumi
authors.initials: H
authors.lastname: Kasai
authors.affiliation: Clinical Study Management Division, Bell Medical Solutions Inc, Tokyo, Japan.
authors.forename: Makoto
authors.initials: M
authors.lastname: Suda
authors.affiliation: Department of Anesthesiology and Critical Care Medicine, Asahikawa Medical University, Hokkaido, Japan.
authors.forename: Manabu
authors.initials: M
authors.lastname: Yoshimura
authors.affiliation: Department of Anesthesiology and Critical Care Medicine, Asahikawa Medical University, Hokkaido, Japan.
authors.forename: Ami
authors.initials: A
authors.lastname: Sugawara
authors.affiliation: Department of Anesthesiology and Critical Care Medicine, Asahikawa Medical University, Hokkaido, Japan.
authors.forename: Yuki
authors.initials: Y
authors.lastname: Izumi
authors.affiliation: Department of Anesthesiology and Critical Care Medicine, Asahikawa Medical University, Hokkaido, Japan.
authors.forename: Takafumi
authors.initials: T
authors.lastname: Iida
authors.affiliation: Department of Anesthesiology and Critical Care Medicine, Asahikawa Medical University, Hokkaido, Japan.
authors.forename: Atsushi
authors.initials: A
authors.lastname: Kurosawa
authors.affiliation: Department of Anesthesiology and Critical Care Medicine, Asahikawa Medical University, Hokkaido, Japan.
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Iwasaki
keywords: men; pharmacokinetic model; phosphodiesterase III inhibitor