AbstractThe 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 24h after treatment was studied using data from 49 patients treated with 201600mg/m2 carboplatin as a 60100min infusion (median 60min). 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 24h (median 24.4; range 16.327.3h) total plasma Pt concentration (M) and free carboplatin AUC (mg/ml.min): AUC=(24h Pt+0.3)/0.82 (r2=0.93, AUC median 5.8 (0.1328)mg/ml.min, 24h Pt median 4.4 (0.123) M). A similar relationship was observed in vitro [AUC=(24h Pt +0.1)/0.93 (r2=0.98, AUC median 7.9 (2.017) mg/ml.min, 24h Pt median 7.1 (1.815) M)]. The relationship derived from the in vivo data gave an unbiased and reasonably accurate estimate of the measured carboplatin AUC in 13 patients (AUC=5.18.7 mg/ml.min, GFR=59129ml/min, infusion time 3045 min, 24h sampling time 22.924.5h), 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 24h 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.