Clinical pharmacokinetics of vindesine infusion

Fifteen patients were given vindesine (VDS) either by iv bolus injections at doses ranging from 0.7 to 1.2 mg/m2 or by 5-day infusions (total dose: 5 mg/m2), in combination with cisplatin (20 mg/m2/day) and bleomycin (6 mg/m2/day) for 5 days. For bolus injections, the total dose of VDS in one treatment was completed to 5 mg/m2 by infusion on Days 4 and 5. Drug concentrations in plasma and urine were measured by radioimmunoassay. Plasma concentration decay curves after bolus injection presented the expected triphasic shape, whereas for infusions, plasma concentrations increased and reached steady-state after about 30 hours and declined in a biphasic way after infusion discontinuation. Steady-state concentrations ranged from 4 to 15 micrograms/L and showed important variations among patients. Clearances estimated from the area under the concentration-time curves were significantly smaller for infusions than for bolus injections. This observation was interpreted as an indication of VDS pharmacokinetic nonlinearity. Terminal half-lives and renal clearances were not significantly different for the two types of administration. Toxicity of the treatment was generally limited, except for one major renal failure; two patients showed objective tumor regression after therapy.