Pharmacokinetic study of VM26 given as a prolonged IV infusion to ovarian cancer patients

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Abstract
Plasma levels of VM26 were assayed by HPLC in six ovarian cancer patients with normal renal and liver function who received the drugs as an initial 1-h IV infusion of 80 mg/m2 followed by a 24-h IV infusion of 120 mg/m2. These doses and infusion rates were chosen on the basis of mean VM26 clearance values found in a previous study, with the aim of reaching plasma steady-state levels of approximately 6 μg/ml in a short time. Plasma steady-state levels of 4–10 μg/ml, close to those predicted theoretically, were in fact attained at 4–9 h during the second, slower infusion. Mean half-lives and clearance values were 8.6±1.1 h and 0.78±0.08 l/h/m2. Six percent of the VM26 dose was recovered as unchanged drug in the urines collected up to 24 h after the end of infusion. The glucuronide of VM26 aglycone (4′-demethylepipodophyllotoxin) was identified in the urine of all patients, in amounts corresponding to about 8% of the drug dose.