Pharmacokinetic evaluation of increasing dosages of etoposide in a chronic hemodialysis patient

Abstract

A chronic hemodialysis patient was treated for small cell lung cancer with a combination therapy consisting of doxorubicin, cyclophosphamide, and etoposide. The dose of etoposide was increased to normal in five steps because of the possible accumulation and higher plasma peak levels due to terminal renal failure. In order to study this phenomenon, plasma, urine, and dialysate levels of etoposide were determined during five treatment courses with a high-performance liquid chromatographic method combined with electrochemical detection; this proved that the pharmacokinetic curves for etoposide fit a two-compartment model. Peak plasma levels were 7.96, 10.84, 18.24, 21.0, and 24.0 micrograms/ml for dosages of etoposide of 75, 100, 150, 200, and 250 mg, respectively. No accumulation occurred, half-life times of the elimination phase were between 8.7 and 23.0 hours, apparent distribution volumes of the central compartment were between 9.2 and 14.5 L, and the total-body clearances were between 2.1 and 2.8 L/hour. Thus, pharmacokinetic parameters were comparable with those obtained in patients with normal renal function. Hemodialysis did not disturb the exponential decay of plasma etoposide concentration during the elimination phase. No etoposide was found in the dialysate and only minimal etoposide was recovered from the urine. The data presented here indicate that renal clearance is not indispensable for eliminating etoposide.