PHARMACOKINETICS OF VINDESINE GIVEN AS AN INTRAVENOUS BOLUS AND 24-HOUR INFUSION IN HUMANS

  • 1 January 1985
    • journal article
    • research article
    • Vol. 45  (1) , 464-469
Abstract
The pharmacokinetics of vindesine was examined after the determination of serum drug levels by radioimmunoassay in patients who received the drug either as an i.v. bolus or a 24-h infusion. After i.v. bolus, vindesine was eliminated from the serum by triphasic decay. The central compartment was .apprx. 6 times the serum volume. The peak serum level achieved by i.v. bolus was .apprx. 16 times that achieved by the 24-h infusion. The post-24 h-infusion serum decay followed biphasic decay. Pharmacokinetic modeling, assuming a prolonged infusion period, resulted in a triphasic decay curve, with an extremely short distribution phase which would not be clinically detectable. This was due to the incorporation of the distribution phase into the infusion period. This explains the experimental data of a biphasic decay curve observed after 24-h infusion. Pharmacokinetic parameters for the 2 phases observed after 24-h infusion were similar to values calculated from i.v. bolus data. The c .times. t for 24-h infusion was identical to that after i.v. bolus; theoretically, the c .times. t appears constant regardless of infusion time. The rate of elimination and/or the c .times. t, rather than the peak serum level, evidently played a role in the degree of hematological toxicity. [The use of this as an antineoplastic drug was outlined.].