A limited sampling strategy for determining carboplatin AUC and monitoringdrug dosage

There are several convincing reports showing relationships between the area under the curve of ultrafilterable concentration versus time (AUC) and pha rmacodynamics of carboplatin. It is advisable, in treated patients, to chec k the AUC that is effectively delivered as compared with the prescribed AUG . To this. end, Limited sampling strategy seems to be an adequate approach since it limits the constraints of repeated blood sampling for both patient s and nursing staff. A flexible limited sampling method for assessing ultra filterable carboplatin AUC was developed. This method was based on a Bayesi an estimation of carboplatin clearance using the NON linear Mixed Effect Mo del (NONMEN) program and a large pharmacokinetic and covariates database (1 03 patients). The optimal sampling design was a two-sample schedule (1 and 4 h after the end of infusion). During a prospective evaluation. it allowed an adequate estimation of carboplatin clearance with a non-significant bin s (-4.5%) and a good precision (9%). In a second stage, this method was cli nically applied to monitor carboplatin AUC in a group of 5 patients with me tastatic germ cell rumours treated with intensified high dose carboplatin-b ased chemotherapy for 3 days. Dosage adjustments were performed according t o daily controls of their AUC in order to obtain a total AUC of 20 mg/ml x min. By using this strategy all patients effectively received a total AUC v ery close to this targeted AUC, thus proving the clinical usefulness of thi s limited sampling method. (C) 2000 Elsevier Science Ltd. All rights reserv ed.