Carboplatin pharmacokinetics in patients receiving carboplatin and paclitaxel/docetaxel for advanced lung cancers: impact of age and renal function on area under the curve.
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.
Kern
W
W
University Hospital Grosshadern, Department of Medicine III, Ludwig Maximilians University, München, Germany. wolfgang.kern@med3.med.uni-muenchen.de
Braess
J
J
Friedrichsen
S
S
Kaufmann
C C
CC
Schleyer
E
E
Hiddemann
W
W
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
D000970:Antineoplastic Agents; D000972:Antineoplastic Agents, Phytogenic; D043823:Taxoids; D000077143:Docetaxel; D016190:Carboplatin; D017239:Paclitaxel