The absolute oral bioavailability of etoposide (VePesid) was determined in cancer patients based on a comparison of intravenous and oral administration. The oral dosage unit was etoposide solubilized in a polyethylene glycol-based vehicle in a soft gelatin capsule formulation. The intravenous dose was 80 mg/m2 as a one-hour infusion and the oral dose was 160 mg/m2. The absolute bioavailability based on plasma concentrations or urinary excretion of etoposide was 48% to 57%. The plasma elimination half-life was 5.3 hours, total body clearance 21.4 mL/min/m2, and renal clearance 7.7 mL/min/m2. Significant intersubject and intrasubject variation was observed in intravenous and oral pharmacokinetics and oral bioavailability. This variability could be related to intrapatient and interpatient differences in nonrenal clearance and the inherent patient and disease status problems in evaluating the pharmacokinetics of anticancer drugs. This variability is characteristic of many classes of cytotoxic drugs and indicative of the requirements of individual dose optimization.