A single-sample assay for the estimation of the area under the free carboplatin plasma concentration versus time curve

Abstract

The aim of this study was to develop and validate a simple and rapid method for the estimation of the area under the free carboplatin plasma concentration versus time curve (AUC). The relationship between the carboplatin AUC and the total plasma platinum (Pt) concentration 24 h after treatment was studied using data from 49 patients treated with 20–1600 mg/m² carboplatin as a 60–100 min infusion (median 60 min). The relationship was confirmed by the in vitro incubation of carboplatin in human plasma and prospectively validated in 13 ovarian cancer patients. Free carboplatin was separated by ultrafiltration (MW cut off 30,000), and free and total Pt measured by atomic absorption spectrophotometry. There was a linear relationship in vivo between the 24 h (median 24.4; range 16.3-27.3 h) total plasma Pt concentration (µM) and free carboplatin AUC (mg/ml.min): AUC =(24 h Pt+0.3)/0.82 (r² =0.93, AUC median 5.8 (0.13-28)mg/ml.min, 24 h Pt median 4.4 (0.1-23) µM). A similar relationship was observed in vitro [AUC =(24 h Pt + 0.1)/0.93 (@#@ r² =0.98, AUC median 7.9 (2.0-17) mg/ml.min, 24 h Pt median 7.1 (1.8-15) µM)]. The relationship derived from the in vivo data gave an unbiased and reasonably accurate estimate of the measured carboplatin AUC in 13 patients (AUC =5.1-8.7 mg/ml.min, GFR =59-129 ml/min, infusion time 30–45 min, 24 h sampling time 22.9-24.5 h), giving a percentage mean error of -4.2% and root mean squared percentage error of 11.5%. These results show that the analysis of a single blood sample taken 24 h after carboplatin administration can be used to produce an unbiased and reasonably accurate measure of the free carboplatin AUC. Unlike published limited sampling strategies, this method is not complicated by the need to accurately control the duration of the carboplatin infusion or the time at which the sample is taken.