Pharmacokinetics of vincristine in cancer patients treated with nifedipine

• Published in: Cancer Vol. 64; no. 9; pp. 1805 - 1811
• Main Authors: Fedeli, Leone, Colozza, Mariantonietta, Boschetti, Enrico, Sabalich, Isabella, Aristei, Cynthia, Guerciolini, Roberto, Del Favero, Albano, Rossetti, Riccardo, Tonato, Maurizio, Rambotti, Pietro, Davis, Stephen
• Format: Journal Article Conference Proceeding
• Language: English
• Published: New York Wiley Subscription Services, Inc., A Wiley Company 01.11.1989; Wiley-Liss
• Subjects: Aged; Antineoplastic agents; Antineoplastic Combined Chemotherapy Protocols; Biological and medical sciences; Blood Chemical Analysis; Chemotherapy; Female; Humans; Male; Medical sciences; Metabolic Clearance Rate; Middle Aged; Neoplasms - drug therapy; Nifedipine - administration & dosage; Nifedipine - therapeutic use; Pharmacology. Drug treatments; Radioimmunoassay; Regression Analysis; Vincristine - administration & dosage; Vincristine - adverse effects; Vincristine - pharmacokinetics; Antineoplastic agent; Human; Intravenous administration; Calcium antagonist; Drug interaction; Malignant tumor; Pharmacokinetics
• ISSN: 0008-543X; 1097-0142
• DOI: 10.1002/1097-0142(19891101)64:9<1805::AID-CNCR2820640908>3.0.CO;2-D

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 T1/2α was shorter in NIF‐treated patients, whereas the T 1/2γ was longer in the NIF‐treated group. The NIF‐treated group showed an increase in the AUC O‐∞ 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.