title: Population pharmacokinetic analysis of panipenem/betamipron in patients with various degrees of renal function.
abstract: BACKGROUND
  Although plasma concentrations of panipenem were elevated and the risk of adverse events would increase in patients with renal impairment, a precise dosage regimen for patients with renal impairment has not been established.
  
  
  METHODS
  Population pharmacokinetic analyses were performed with plasma concentrations from 26 healthy volunteers and 41 patients. Optimal dosage regimens for patients with renal impairment were determined based on the bacteriostatic index of C(20%T)>(MIC), the concentration corresponding to the time above MIC of 20% of the dosing interval.
  
  
  RESULTS
  The clearance of panipenem and betamipron was correlated with creatinine clearance and the volume of the distribution of panipenem was correlated with body weight. C(20%T)>(MIC) for a standard dosage regimen of panipenem was 4.3 microg/ml, and the optimal dosage regimen for the patients was established based on this value.
  
  
  CONCLUSIONS
  The dosage regimen of panipenem for patients with renal impairment should be reduced when creatinine clearance is lower than 60 ml/min.
authors.affiliation: Clinical Pharmacology and Biostatistics Department, Sankyo Co., Tokyo, Japan. tajima_naoyuki@sankyo.co.jp
authors.forename: Naoyuki
authors.initials: N
authors.lastname: Tajima
authors.forename: Hitoshi
authors.initials: H
authors.lastname: Ishizuka
authors.forename: Hideo
authors.initials: H
authors.lastname: Naganuma
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000409:Alanine / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000493:pharmacokinetics; D019540:Area Under Curve; D002851:Chromatography, High Pressure Liquid; D003404:Creatinine / Q000378:metabolism; D006193:Haemophilus influenzae / Q000187:drug effects; D006801:Humans; D007677:Kidney Function Tests; D008657:Metabolic Clearance Rate; D008875:Middle Aged; D051437:Renal Insufficiency / Q000453:epidemiology / Q000378:metabolism* / Q000503:physiopathology; D013845:Thienamycins / Q000008:administration & dosage / Q000493:pharmacokinetics*
chemical_list: D013845:Thienamycins; C047207:N-benzoylalanine; D003404:Creatinine; D000409:Alanine; C039536:panipenem