Pharmacokinetics of vincristine in cancer patients treated with nifedipine.
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.
Fedeli
L
L
Servizio di Medicina Nucleare, Università-Policlinico, Perugia, Italy.
Colozza
M
M
Boschetti
E
E
Sabalich
I
I
Aristei
C
C
Guerciolini
R
R
Del Favero
A
A
Rossetti
R
R
Tonato
M
M
Rambotti
P
P
D000368:Aged; D000971:Antineoplastic Combined Chemotherapy Protocols; D001774:Blood Chemical Analysis; D005260:Female; D006801:Humans; D008297:Male; D008657:Metabolic Clearance Rate; D008875:Middle Aged; D009369:Neoplasms / Q000188:drug therapy*; D009543:Nifedipine / Q000008:administration & dosage / Q000627:therapeutic use*; D011863:Radioimmunoassay; D012044:Regression Analysis; D014750:Vincristine / Q000008:administration & dosage / Q000009:adverse effects / Q000493:pharmacokinetics*
D014750:Vincristine; D009543:Nifedipine