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

Purpose: To further define the most appropriate way of choosing the dose of carboplatin. Patients and methods: The pharmacokinetics of carboplatin wer e 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 deter mined by flameless atomic absorption spectrometry. A multiple regression an alysis was performed for interactions between pharmacokinetic parameters an d protreatment characteristics. Results: Using a two-compartment-model, the following parameters were obtained (mean, coefficient of variation): initi al half-lifer 0.903 h (48%); terminal half-life, 13.6 h (116%); maximum pla sma concentration (C-max), 38.5 muM (86%); AUC 111.9 muM/h (86%); volume of distribution, 411 1 (130%); total clearance (C-t), 579 ml/min (75%); renal clearance (C-r), 453 ml/min (80%); renal elimination, 76% of dose (17%). I n 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 crcatinine (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 drug s 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: Th ese data stress the importance of dosing carboplatin according to renal fun ction and age and warrant further analyses to validate this concept prospec tively.