CISPLATIN PHARMACOKINETICS IN CHILDREN WITH CANCER

Cisplatin is an important drug in the treatment of a number of paediat ric cancers yet, despite widespread use, there are only very limited d ata on the pharmacokinetics of the drug in children. Cisplatin pharmac okinetics were studied in 21 patients following a 24 h infusion of 50- 120 mg/m(2) cisplatin. Total and free platinum (Pt) levels in plasma a nd Pt in urine, were measured by atomic absorption spectrophotometry. Pharmacokinetic parameters were determined by non-compartmental and co mpartmental analyses. There was 3-fold interpatient variability in fre e drug exposure (area under the plasma concentration versus time curve - AUC) for a given surface area-based dose of cisplatin. The mean (+/ - SD) pharmacokinetic parameters for free Pt were: AUC 0.47 +/- 0.13 m g/ml.min/100 mg/m(2), V-dss 12.5 +/- 2.7 l/m(2), t(1/2) 39 +/- 9 min, Ke 0.019 +/- 0.006 min(-1), Cl-renal 62 ml/min/m(2), Cl-total 233 +/- 455 ml/min/m(2), Cp-ss 0.31 +/- 0.09 mu g/ml. The total free Pt cleara nce was 1.5-5.8-fold higher (3.4 +/- 1.0) than the glomerular filtrati on rate (GFR). The renal clearance of cisplatin was not related to GFR and cisplatin was subject to only limited urinary excretion (27% admi nistered dose 0-48 h), indicating that there are other important pathw ays of clearance beside renal elimination. Patient and treatment heter ogeneity pre eluded the investigation of pharmacokinetic-pharmacodynam ic relationships; however, the degree of interpatient pharmacokinetic variability observed suggests that body surface area-based dosing of c isplatin in children is not satisfactory. (C) 1997 Elsevier Science Lt d.