Prediction of therapeutic effect of rasburicase on hyperuricemia associated with chemotherapy based on theoretical model

Abstract

Rasburicase has a strong and fast effect for reducing blood levels of uric acid. However, there have been no reports of theoretical analysis for the rational dose and interval of administration. Thus we constructed a pharmacokinetic and pharmacodynamic model to determine changes in uric acid level after rasburicase administration at various doses and regimens. The time courses of uric acid level predicted using our model were in good agreement with observed data, indicating adequate performance for our model. The therapeutic effects after a single infusion at various rates of generation of uric acid were predicted. The maximum effect was not a large difference, in spite of the generation rate. Then, the therapeutic effects of repeated administrations were predicted. The effect did not change when rasburicase was administered at more than the usual dose. Besides, as the administration interval increased, the difference between minimum and maximum level of uric acid became greater. However, in all doses and regimens, adequate therapeutic effects were obtained. In conclusion, the model was found useful for predicting therapeutic effect of rasburicase and individually determining rational dosage regimen of rasburicase.