title: Population pharmacokinetics and pharmacodynamics of biapenem in paediatric patients.
abstract: OBJECTIVE
  To develop a population pharmacokinetic model for biapenem in paediatric patients and to use the parameter estimates to assess pharmacodynamic exposure of common bacterial populations.
  
  
  METHODS
  Biapenem plasma concentrations (n = 125) from 25 paediatric patients were analysed using nonmem. The parameter estimates were used in a Monte Carlo simulation to predict the exposure time during which the drug concentration remains above the minimum inhibitory concentration.
  
  
  RESULTS
  A two-compartment model fitted the data, and creatinine clearance (CL(cr)) and total body weight (TBW) were the most significant covariates. The final model was CL (L/h) = 0.0458 x CL(cr), V(c) (L) = 0.162 x TBW, Q (L/h) = 2.05, V(p) (L) = 1.73, where CL is the clearance, V(c) is the volume of distribution of the central compartment, Q is the intercompartmental clearance and V(p) is the volume of distribution of the peripheral compartment. Biapenem regimens of 5 mg/kg q8h and 10 mg/kg q8h provided sufficient pharmacodynamic exposures to Pseudomonas aeruginosa and Streptococcus pneumoniae in most typical patient populations.
  
  
  CONCLUSIONS
  These results better define the pharmacokinetics of biapenem and help in the choice of the appropriate dosage regimens for paediatric.
authors.affiliation: Department of Clinical Pharmacotherapy, Hiroshima University, Hiroshima, Japan. ikawak@hiroshima-u.ac.jp
authors.forename: K
authors.initials: K
authors.lastname: Ikawa
authors.forename: N
authors.initials: N
authors.lastname: Morikawa
authors.forename: K
authors.initials: K
authors.lastname: Ikeda
authors.forename: M
authors.initials: M
authors.lastname: Miki
authors.forename: S
authors.initials: S
authors.lastname: Nishimura
authors.forename: M
authors.initials: M
authors.lastname: Kobayashi
mesh_terms: D000293:Adolescent; D000900:Anti-Bacterial Agents / Q000097:blood / Q000493:pharmacokinetics* / Q000494:pharmacology; D001424:Bacterial Infections / Q000097:blood / Q000188:drug therapy; D001835:Body Weight; D002648:Child; D002675:Child, Preschool; D003404:Creatinine / Q000097:blood; D005260:Female; D006801:Humans; D007223:Infant; D008297:Male; D008826:Microbial Sensitivity Tests; D008954:Models, Biological; D009010:Monte Carlo Method; D011550:Pseudomonas aeruginosa / Q000187:drug effects; D013296:Streptococcus pneumoniae / Q000187:drug effects; D013845:Thienamycins / Q000097:blood / Q000493:pharmacokinetics* / Q000494:pharmacology
chemical_list: D000900:Anti-Bacterial Agents; D013845:Thienamycins; D003404:Creatinine; C065257:biapenem