TEST DOSE-GUIDED ADMINISTRATION OF CISPLATIN IN AN ANEPHRIC PATIENT -A CASE-REPORT

Background: Although cisplatin pharmacokinetics is well documented in patients with various degrees of renal dysfunction, no information is available concerning cisplatin administration to anephric patients. Si nce anephric patients may sometimes need cisplatin therapy, it is ther efore of importance to define therapeutic guidelines for cisplatin adm inistration in this patient population. Patient and methods: Cisplatin was administered to an anephric patient (bilateral nephrectomy) requi ring 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 f lameless atomic absorption spectrophotometry. Haemodialysis was starte d 30 min before the beginning of the cisplatin infusion and was mainta ined for 4 h thereafter. Results: Under haemodialysis, filterable and total platinum pharmacokinetics after the test dose were comparable wi th a patient with normal renal function, i.e. with peak plasma concent rations of 126 ng/ml and 166 ng/ml for the filterable and the total pl atinum, 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 term inal half-lives of filterable and total platinum were 0.42 h and 101 h , respectively. Based on the test dose platinum pharmacokinetics, a th erapeutic dose of 100 mg (63 mg/m2) of cisplatin was administered. Fol lowing the therapeutic dose, peak plasma concentrations reached 1,120 ng/ml for the filterable and 1,280 ng/ml for the total platinum. The A UCs were 1,609 and 65,556 ng.h/ml for the filterable and the total pla tinum, 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 d ose, 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 . Conclusion: This approach may be helpful in monitoring cisplatin the rapy in similar cases requiring cisplatin administration.