Impact of the biochemical assay for serum creatinine measurement on the individual carboplatin dosing:: A prospective study

We preciously developed a formula to estimate the individual carboplatin clearance (CL) based on serum creatinine (Scr) determined by an enzymatic assay using creatinine amidohydrolase. An analytical comparison had shown systematic differences between this method and the commonly used Jaffe method (with Jaffe Scr (in muM) (-)1.08x enzymatic Scr (+)1.6. as regression equation). We performed a pharmacokinetic prospective clinical study using the Jaffe assay to evaluate the impact of the method used for Scr measurement on the prediction of the carboplatin CL. In forty patients, carboplatin dosing was performed according to the Chatelut formula where the serum creatinine level was corrected according to the above equation. The population pharmacokinetics of carboplatin were analysed using the NONMEM program to determine the individual carboplatin CL from a limited sampling strategy. Thanks to the correction of the Jaffe Scr, no significant difference was observed between the administered and the optimal dose. In contrast, if no correction of the Scr was done the patients would have been significantly under-dosed. Moreover, a covariate analysis using NONMEM gave a verb consistent result showing that Scr should be decreased by 11.6% A hen the Jaffe value is used within the Chatelut equation. This study confirmed that differences in the Scr assay has consequences with regard to carboplatin dosing. The correction e propose For Scr obtained by the Jaffe method may help to standardise clinical practice. (C) 2002 Elsevier Science Ltd. All rights reserved.