Pharmacokinetics of vincristine in cancer patients treated with nifedipine

Vincristine (VCR) is an antitumor drug which exerts its action by interfering with the reproductive apparatus of cells. The use of vincristine is complicated by its toxicity, particularly for the nervous system, and resistance to the drug. Although VCR resistance seems to arise from a number of different causes, it is believed to be related to a decrease in the accumulation of vincristine inside the cells. Tissue culture experiments using human cells and experiments in mice have indicated that the use of calcium entry blockers such as nifedipine (NIF) can increase the cytotoxic effect of VCR. The combined use of VCR and NIF may yield improved results in the treatment of certain cancers. Before beginning formal studies, the pharmacokinetics of VCR with and without NIF were measured. Twenty-six patients with a variety of solid tumors were injected with 2 milligrams (mg) of VCR; 12 patients received 10 mg of NIF three times daily three days before and seven days after VCR. Blood samples were taken after VCR injection, and a sensitive radioimmunoassay was used to measure the concentration of VCR in the blood. The results indicated that the presence of NIF increased the rate at which VCR was distributed in the tissues, and decreased the rate at which it was eliminated from the body. The excretion of VCR in the urine was significantly reduced in the presence of NIF. Although the use of NIF may improve the efficacy of VCR in treating cancer, it might also increase VCR toxicity. Appropriate care should be taken in designing treatment protocols in VCR and NIF clinical trials. (Consumer Summary produced by Reliance Medical Information, Inc.)