Limited-sampling models for estimation of the carboplatin area under the curve

Background: The area under the curve (AUG) of free carboplatin, is a major determinant of toxicity and response. A conventional pharmacokinetic study to determine AUC requires frequent blood sampling. One strategy for overcoming this problem is to apply a limited sampling model (LSM). Materials and methods: We developed LSMs by stepwise forward multiple regression analysis using 27 data series from 24 patients with lung cancer (training data set) who received carboplatin in combination with oral etoposide. The models were then validated using 24 data series from 18 patients (test data set). Results: In the test data set, the single-sample model was confirmed to give excellent estimation of the AUC: AUC (mg/ml x min) = 0.93 x C-3h + 0.47 (MPE% = 4.4%, RMSE% = 8.9%). Furthermore, the two-sample model was shown to improve both the bias and precision of AUC estimation: AUC = 0.16 x C-1h + 2.26 x C-8h + 0.75 (MPE% = 0.9%, RMSE% = 5.3%). Conclusions: Our models are useful for future trials to define the accurate relationships between the dose-intensity and effect of carboplatin.