title: [Population pharmacokinetics applied to optimising cisplatin doses in cancer patients].
abstract: OBJECTIVE
  To develop and internally validate a population pharmacokinetics model for cisplatin and assess its prediction capacity for personalising doses in cancer patients.
  
  
  METHODS
  Cisplatin plasma concentrations in forty-six cancer patients were used to determine the pharmacokinetic parameters of a two-compartment pharmacokinetic model implemented in NONMEN VI software. Pharmacokinetic parameter identification capacity was assessed using the parametric bootstrap method and the model was validated using the nonparametric bootstrap method and standardised visual and numerical predictive checks. The final model's prediction capacity was evaluated in terms of accuracy and precision during the first (a priori) and second (a posteriori) chemotherapy cycles.
  
  
  RESULTS
  Mean population cisplatin clearance is 1.03 L/h with an interpatient variability of 78.0%. Estimated distribution volume at steady state was 48.3 L, with inter- and intrapatient variabilities of 31,3% and 11,7%, respectively. Internal validation confirmed that the population pharmacokinetics model is appropriate to describe changes over time in cisplatin plasma concentrations, as well as its variability in the study population. The accuracy and precision of a posteriori prediction of cisplatin concentrations improved by 21% and 54% compared to a priori prediction.
  
  
  CONCLUSIONS
  The population pharmacokinetic model developed adequately described the changes in cisplatin plasma concentrations in cancer patients and can be used to optimise cisplatin dosing regimes accurately and precisely.
authors.affiliation: Unidad de Farmacia y Tecnología Farmacéutica, Departamento de Ingeniería, Universidad Miguel Hernández de Elche, Alicante, España.
authors.forename: A
authors.initials: A
authors.lastname: Ramón-López
authors.forename: V
authors.initials: V
authors.lastname: Escudero-Ortiz
authors.forename: V
authors.initials: V
authors.lastname: Carbonell
authors.forename: J J
authors.initials: JJ
authors.lastname: Pérez-Ruixo
authors.forename: B
authors.initials: B
authors.lastname: Valenzuela
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000465:Algorithms; D000970:Antineoplastic Agents / Q000008:administration & dosage* / Q000493:pharmacokinetics* / Q000627:therapeutic use; D002945:Cisplatin / Q000008:administration & dosage* / Q000493:pharmacokinetics* / Q000627:therapeutic use; D004305:Dose-Response Relationship, Drug; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D015233:Models, Statistical; D009369:Neoplasms / Q000188:drug therapy / Q000378:metabolism*; D012984:Software; D055815:Young Adult
chemical_list: D000970:Antineoplastic Agents; D002945:Cisplatin