Clinical pharmacology of vinzolidine

Vinzolidine (VZL), a new semisynthetic vinca alkaloid, was studied by using 3H-labeled VZL administered PO in four patients. At single doses from 1.5 to 36.5 mg/m2 (0.034-0.919 mg/kg) radioactivity was rapidly absorbed with a half-life of absorption of 1 h and a peak at 4 h. Plasma decay of radiolabel followed a biphasic pattern with an alpha half-life of 10.48 h and a beta half-life of 172 h. The apparent plasma clearance was dose-dependent. The total radiolabel recovered was 52.9% +/- 11.4% of the administered label, with 90% in the feces. HPLC analysis revealed that in all extracted plasma, urine, and feces the predominant material was unchanged VZL. Several metabolites were observed but not identified.