RADIOIMMUNOASSAY AND PRELIMINARY PHARMACOKINETIC STUDIES IN RATS OF 5'-NORANHYDROVINBLASTINE (NAVELBINE)

  • 1 January 1984
    • journal article
    • research article
    • Vol. 44  (12) , 5609-5613
Abstract
The antitumor drug navelbine (5''-noranhydrovinblastine) was converted into a reactive acid azide and covalently coupled to free amino groups of bovine serum albumin. The conjugate was used to raise specific antibodies in rabbits. The acid azide derivative was also reacted with the peptide glycyl-L-tyrosine and the conjugate was radiolabeled with 125l. The resulting high-specific-activity .gamma.-emitting probe was shown to bind very tightly to anti-navelbine antiserum. Using these reagents, a radioimmunoassay was developed which proved sensitive enough to measure < 10 fmol of navelbine in serum and which showed little cross-reaction with closely related analogs such as vinblastine, vindesinem or 5''-6''-secovinblastine. A preliminary pharmacokinetic analysis was performed in rats given navelbine i.v. (dose, 1.2 mg/kg). The radioimmunoassay was used to monitor the plasma concentration decay kinetics after injection. Navelbine systemic clearance was estimated from the area under the concentration-time curves [1.9 .+-. 0.5 (SD) l/h per kg] and was found to be larger than that of vinblastine (1.1 .+-. 0.4 l/h per kg) measured under similar conditions (dose, 0.6 mg/kg). Terminal half-lives were 8.9 .+-. 2.1 h for navelbine and 8.1 .+-. 2.6 h for vinblastine. This radioimmunoassay will provide a sensitive method with which to monitor plasma levels of navelbine during clinical trials and to further study the relationships between pharmacokinetics, toxicity and antitumor activity amoung Vinca alkaloids.