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

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 (C_max), 38.5 μM (86%); AUC, 111.9 μM/h (86%); volume of distribution, 411 l (130%); total clearance (C_t), 579 ml/min (75%); renal clearance (C_r), 453 ml/min (80%); renal elimination, 76% of dose (17%). In the univariate analysis, age was significantly related to C_max (P=0.0303), AUC (P=0.0050), C_t (P=0.0020), C_r (P=0.0092). Plasma creatinine (Cr_p) was related to C_max (P=0.0228), and 1/[Cr_p] was related to C_max (P=0.0015) and AUC (P=0.0054), while body weight was related to C_max (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/[Cr_p] (P < 0.01) and age (P < 0.01). Cr_p (P < 0.05) and 1/[Cr_p] (P < 0.01) were significantly associated with C_max. Conclusions: These data stress the importance of dosing carboplatin according to renal function and age and warrant further analyses to validate this concept prospectively.