Pharmacokinetics of high dose etoposide (VP 16-213)

This paper describes the pharmacokinetics of etoposide in cancer patients after high dose administration (up to 3.5 g/m2). High performance liquid chromatography with electrochemical detection was used to determine etoposide, cis etoposide and the glucuronide of etoposide in plasma, bile, cerebro-spinal fluid, urine, saliva and ascites, the detection limit being 2 ng etoposide/ml plasma. The plasma concentration time curve shows a tri-phasic decay. The terminal phase is very slow. It was concluded that etoposide is strongly bound in the peripheral compartment. The volume of the central compartment varied from 7.4 to 20.1 l and the steady state volume of distribution from 3.1 to 7.8 l/m2. Relatively high concentrations of etoposide were found in saliva, bile, ascites and urine and low concentrations in cerebro-spinal fluid. The total body clearance varied from 12.0 to 26.8 ml/min/m2, and 26.2 to 53.4% was excreted as unchanged etoposide into the urine and 8.3 to 17.3% as glucuronide into the urine. Very low amounts of the trans hydroxy acid of etoposide and the cis etoposide were detected in the urine. Glucuronides were found in urine and duodenal fluid but not in plasma.