LIMITED-SAMPLING MODELS FOR ESTIMATION OF THE CARBOPLATIN AREA-UNDER-THE-CURVE

Background: The area under the curve (AUG) of free carboplatin, is a m ajor determinant of toxicity and response. A conventional pharmacokine tic study to determine AUC requires frequent blood sampling. One strat egy for overcoming this problem is to apply a limited sampling model ( LSM). Materials and methods: We developed LSMs by stepwise forward mul tiple regression analysis using 27 data series from 24 patients with l ung cancer (training data set) who received carboplatin in combination with oral etoposide. The models were then validated using 24 data ser ies from 18 patients (test data set). Results: In the test data set, t he single-sample model was confirmed to give excellent estimation of t he 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 do se-intensity and effect of carboplatin.