title: Carboplatin pharmacokinetics in patients receiving carboplatin and paclitaxel/docetaxel for advanced lung cancers: impact of age and renal function on area under the curve.
abstract: OBJECTIVE
  To further define the most appropriate way of choosing the dose of carboplatin.
  
  
  METHODS
  The pharmacokinetics of carboplatin were analyzed in 30 patients with advanced lung cancer receiving a total of 48 cycles of carboplatin plus paclitaxel/ docetaxel combination chemotherapy. Platin concentrations of ultrafiltrated plasma and urine samples were determined by flameless atomic absorption spectrometry. A multiple regression analysis was performed for interactions between pharmacokinetic parameters and pretreatment characteristics.
  
  
  RESULTS
  Using a twocompartment-model, the following parameters were obtained (mean, coefficient of variation): initial half-life, 0.903 h (48%); terminal half-life, 13.6 h (116%); maximum plasma concentration (Cmax), 38.5 microM (86%); AUC, 111.9 microM/h (86%); volume of distribution, 411 l (130%); total clearance (Ct), 579 ml/min (75%); renal clearance (Cr), 453 ml/min (80%); renal elimination, 76% of dose (17%). In the univariate analysis, age was significantly related to Cmax (P = 0.0303), AUC (P = 0.0050), Ct (P = 0.0020), Cr (P = 0.0092). Plasma creatinine (Crp) was related to Cmax (P = 0.0228), and 1/[Crp] was related to Cmax (P = 0.0015) and AUC (P = 0.0054), while body weight was related to Cmax (P = 0.0365). No interaction with the schedule of application of the two drugs was observed. In the multivariate analysis, factors significantly related to AUC were 1/[Crp] (P < 0.01) and age (P < 0.01). Crp (P < 0.05) and 1/[Crp] (P < 0.01) were significantly associated with Cmax.
  
  
  CONCLUSIONS
  These data stress the importance of dosing carboplatin according to renal function and age and warrant further analyses to validate this concept prospectively.
authors.affiliation: University Hospital Grosshadern, Department of Medicine III, Ludwig Maximilians University, München, Germany. wolfgang.kern@med3.med.uni-muenchen.de
authors.forename: W
authors.initials: W
authors.lastname: Kern
authors.forename: J
authors.initials: J
authors.lastname: Braess
authors.forename: S
authors.initials: S
authors.lastname: Friedrichsen
authors.forename: C C
authors.initials: CC
authors.lastname: Kaufmann
authors.forename: E
authors.initials: E
authors.lastname: Schleyer
authors.forename: W
authors.initials: W
authors.lastname: Hiddemann
mesh_terms: D000328:Adult; D000367:Age Factors; D000368:Aged; D000970:Antineoplastic Agents / Q000493:pharmacokinetics; D000972:Antineoplastic Agents, Phytogenic / Q000627:therapeutic use; D019540:Area Under Curve; D016190:Carboplatin / Q000493:pharmacokinetics*; D000077143:Docetaxel; D005260:Female; D006801:Humans; D007668:Kidney / Q000187:drug effects*; D007700:Kinetics; D008175:Lung Neoplasms / Q000188:drug therapy*; D008297:Male; D008875:Middle Aged; D017239:Paclitaxel / Q000031:analogs & derivatives* / Q000627:therapeutic use*; D012044:Regression Analysis; D013054:Spectrophotometry, Atomic; D043823:Taxoids; D013997:Time Factors
chemical_list: D000970:Antineoplastic Agents; D000972:Antineoplastic Agents, Phytogenic; D043823:Taxoids; D000077143:Docetaxel; D016190:Carboplatin; D017239:Paclitaxel