ABSTRACT
This paper reports a specific and sensitive enzyme-linked immunosorbent assay (ELISA) for pharmacokinetic studies of vindesine (VDS). Anti-VDS antibody was obtained by immunizing rabbits with VDS conjugated with bovine serum albumin using N-[ß-(4-diazophenyl) ethyl] maleimide as a heterobifunctional coupling agent. An enzyme marker was similarly prepared by coupling VDS with horseradish peroxidase using N-(4-diazophenyl) maleimide. The detection limit of VDS by ELISA was approximately 24 pg/mL with 50-mL samples. This assay was specific for VDS and showed very slight cross-reactivity with other vinca alkaloids, vincristine (0.18%) and vinblastine (0.11%). The values for the VDS concentrations detected using this assay were comparable with those detected using HPLC. There was a good correlation between the values determined by the two methods. Moreover, ELISA was about 50-fold more sensitive in detecting VDS at lower concentrations. The sensitivity and specificity of ELISA should provide a useful tool for pharmacokinetic studies of VDS.
Subject(s)
Antineoplastic Agents, Phytogenic/blood , Enzyme-Linked Immunosorbent Assay/methods , Vindesine/blood , Animals , Antibodies , Antineoplastic Agents, Phytogenic/pharmacokinetics , Rabbits , Vindesine/immunology , Vindesine/pharmacokineticsABSTRACT
Vindesine (VDS) at a dose of 1.2 mg/m2/day was administered by intravenous drip infusion for five days to advanced breast cancer patients with multiple organ metastases who had developed a clinical resistance to various chemotherapeutic agents. The blood concentration of VDS was determined serially by radioimmunoassay, and the anticancer effect and side effects were evaluated. Of the 31 patients selected for this study, 29 were eligible, and the treatment was effective (complete or partial remission) in 11 (38%). There was, however, no correlation between clinical effects and VDS blood concentration. Continuous VDS administration induced various side effects, but all were controllable. Blood concentration was correlated with side effects. Continuous intravenous administration of VDS is considered to have a therapeutic effect on advanced breast cancer which has developed resistance to multiple-drug therapy including adriamycin.