CLINICAL PHARMACOKINETICS OF VINBLASTINE BY CONTINUOUS INTRAVENOUS-INFUSION

Abstract

Vinblastine (VLB) is moderately active clinically against advanced breast cancer. Since VLB is extensively taken up by platelets, and thus only partially available to tumor cells, an attempt was made to enhance the therapeutic index of VLB by administering by continuous i.v. infusion to patients with advanced breast cancer. Pharmacokinetic studies of generally tritiated VLB were conducted using radiochemical and chromatographic techniques. The elimination of VLB from the plasma of patients who received it by 5-day i.v. infusion at 1-2 mg/sq m daily was biphasic. In 4 patients who achieved partial remission, the average plasma half-life of VLB during the terminal phase was 29.4 .+-. 14.6 days, with a total clearance of 36 .+-. 8 ml/kg per h, and a steady-state apparent volume of distribution of 28.1 .+-. 8.5 l/kg. In 3 patients whose disease merely stabilized, the plasma-half-life was 6.4 .+-. 1.6 days, the total clearance was 137 .+-. 2.9 ml/kg per h, and the volume of distribution was 33.0 .+-. 11.6 l/kg. In 5 patients with refractory disease, these parameters were 2.3 .+-. 0.3 days, 541 .+-. 124 ml/kg per h, and 37.6 .+-. 8.6 l/kg. Since the apparent volumes of distributions at steady state did not differ significantly among these 3 groups, whereas the values of the total clearance were markedly dissimilar, the plasma half-lives of VLB were significantly shorter in patients not responsive to continuous infusion therapy with this drug. It appears that favorable clinical response of patients with advanced breast cancer is associated with slow total clearance of the drug.