Limited sampling model for vinblastine pharmacokinetics.

Abstract

A limited sampling model was developed for vinblastine to estimate the total area under the concentration time curve (AUC) using only two timepoints. Detailed pharmacokinetic analysis (16 timepoints) was performed in 30 patients treated with a small bolus dose (3 mg/m2) of vinblastine. A model for the total AUC was developed by multiple linear regression, using the first 15 patients as the training data set: AUC = 38.0 C10 + 73.8 C36 - 12.9, where C10 and C36 represent the serum vinblastine concentration at 10 hours and 36 hours, respectively (r = 0.99, P less than 0.0001). The model was validated on the other 15 patients, the test data set (r = 0.94, P less than 0.0001), with a mean predictive error of 13%. Limited sampling models may facilitate large-scale pharmacodynamic studies of new anticancer drugs, in order to relate the estimated AUC to toxicity and/or response without the need for detailed pharmacokinetic analysis.