A LIMITED SAMPLING MODEL FOR THE PHARMACOKINETICS OF ETOPOSIDE GIVEN ORALLY

A limited sampling model of etoposide after oral administration to estimate the area under the plasma concentration-time curve from 0 to 24 h (AUC) by determination of the drug plasma levels at only two time points was developed by a multiple regression analysis on a training data set of 15 patients receiving oral doses ranging from 54 to 90 mg/m2. The equation describing the model is AUC (mug ml-1 h) = 5.183 (mug ml-1 h) + 1.193 (h) x C1h (mug/ml) + 8.439 (h) x C4h (mug/ml) (R2 = 0.93, P = 0.0001), where C1h and C4h represent the plasma etoposide concentrations at 1 and 4 h, respectively. The model was validated prospectively on a test data set of 13 patients receiving oral doses ranging from 52 to 87 mg/m2 and, additionally, on a data set of 7 patients receiving oral doses ranging between 176 and 200 mg/m2, investigated in a previous study. Validation on both test data sets gave a relative mean predictive error of 0.1% and a relative root mean square error of 15.8% and 16.7%, respectively. The present study shows that it is possible to obtain a good estimate of the plasma AUC after oral administration of etoposide using a two-time-point sampling model. The model can be used to monitor the etoposide AUC in patients receiving chronic oral treatment.