Test dose-guided administration of cisplatin in an anephric patient: A case report

Abstract

Although cisplatin pharmacokinetics is well documented in patients with various degrees of renal dysfunction, no information is available concerning cisplatin administration to anephric patients. Since anephric patients may sometimes need cisplatin therapy, it is therefore of importance to define therapeutic guidelines for cisplatin administration in this patient population. Cisplatin was administered to an anephric patient (bilateral nephrectomy) requiring cisplatin therapy for a metastatic carcinoma of the urothelium. A test dose of 12 mg (7.5 mg/m2) of cisplatin was first administered as a 1 hour infusion in order to determine the patient's pharmacokinetic parameters. Filterable and total platinum levels were determined by flameless atomic absorption spectrophotometry. Haemodialysis was started 30 min before the beginning of the cisplatin infusion and was maintained for 4 h thereafter. Under haemodialysis, filterable and total platinum pharmacokinetics after the test dose were comparable with a patient with normal renal function, i.e. with peak plasma concentrations of 126 ng/ml and 166 ng/ml for the filterable and the total platinum, respectively. The area under the curves (AUC) were 154 ng.h/ml for the filterable and 11486 ng.h/ml for the total platinum. The terminal half-lives of filterable and total platinum were 0.42 h and 101 h, respectively. Based on the test dose platinum pharmacokinetics, a therapeutic dose of 100 mg (63 mg/m2) of cisplatin was administered. Following the therapeutic dose, peak plasma concentrations reached 1,120 ng/ml for the filterable and 1,280 ng/ml for the total platinum. The AUCs were 1,609 and 65,556 ng.h/ml for the filterable and the total platinum, respectively, as expected from the predicted AUCs obtained from the test dose pharmacokinetics. The terminal half-lives of filterable and total platinum were similar to the ones observed after the test dose, i.e. 0.36 h and 86 h, respectively. Although the patient died of rapidly progressive hepatic failure, the feasibility of the test dose-guided cisplatin administration in an anephric patient is demonstrated. This approach may be helpful in monitoring cisplatin therapy in similar cases requiring cisplatin administration.