The pharmacokinetics of vincristine (VCR) after an intravenous bolus dose of 2 mg were studied in patients with cancer with and without a concomitant treatment with the calcium-entry blocker nifedipine (NIF). VCR concentrations were determined by a sensitive radioimmunoassay. Pharmacokinetic data were analyzed by a nonlinear weighted least-square regression program (SAS-NLIN). A tri-exponential model fitted the raw data better than a bi-exponential model in five of 14 (35%) patients treated with VCR alone and in seven of 12 (58%) patients treated with VCR plus NIF (P = NS). The T1/2 alpha was shorter in NIF-treated patients, whereas the T1/2 gamma was longer in the NIF-treated group. The NIF-treated group showed an increase in the AUC O-infinity and AUC 1 to 96 hours, and a decrease in the AUC 0 to 1 hour. Total plasma clearance of VCR and 7-day urinary excretion of VCR was reduced in the NIF-treated patients. These data suggest that, when VCR is administered to NIF-treated patients with cancer, there is a decrease in VCR clearance from the body. Theoretically, a greater cytotoxicity may be anticipated.
Thirty-three unselected patients with cardiac tamponade secondary to malignant pericardial effusion were treated by intrapericardial instillation of tetracycline hydrochloride. Complete control of the initial signs and symptoms of tamponade was obtained in 30 patients without concomitant chemotherapy or radiotherapy. The procedure did not result in clinically significant complications. Failure of the technique was related to premature removal of the catheter by the patient (one patient) or the inability to totally remove hemorrhagic, clot-filled pericardial fluid (two patients). Survival ranged between 28-704 days and extended survival was related to the performance status and/or chemoradiosensitivity of the primary cancer. No patient successfully treated subsequently developed recurrent cardiac tamponade or alternatively, constrictive pericarditis. Tetracycline pericardial instillation remains a safe, simple, and efficacious treatment of tamponade secondary to malignant disease.
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