Carboplatin pharmacokinetics in patients receiving carboplatin and paclitaxel/docetaxel for advanced lung cancers: impact of age and renal function on area under the curve

摘要

Purpose: To further define the most appropriate way of choosing the dose of carboplatin. Patients and 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 two-compartment-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 μM (86%); AUC, 111.9 μM/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.