Vindesine Verapamil

Vincristine resistance has been studied in Chinese hamster ovary cell lines cells resistant to vincristine also are resistant to vinblastine and vindesine. Suggestions were made that, in cells with relatively low levels of drug resistance, at least two prominent mechanisms of resistance can occur (22). In the first instance, cellular resistance may be attributable to membrane alterations that are reversible, functionally, by treatment with verapamil. In the second, resistance has been postulated to be due to an altered sensitivity of tubulin to the effects of the drugs the primary basis for postulating an altered interaction with tubulin was that a subgroup of cells resistant to vincristine showed enhanced sensitivity to taxol, a drug that can stabilize microtubules. It should be emphasized that differential sensitivities of tubulins from different tumor cells to the effects of vincristine or vinblastine has been proposed as a basis for the susceptibilities of cells to the cytotoxic effects of such drugs (23). Differences have been described in the electrophoretic patterns for tubulins obtained from vin-... 

Cantwell B, Buamah P, Harris AL. Phase I and II study of oral verapamil and intravenous vindesine. Proceedings of the American Society of Clinical Oncology 1985 42 161. 

Fluorouracil Glucocorticoids Indinavir Loperamide Losartan Methotrexate Mitoxantrone Nelfinavir Paclitaxel Ritonavir Saquinavir Sirolimus Tacrolimus Topotecan Vinblastine Vincristine Vindesine Vinorelbine Verapamil ... 

Interfering acenocoumarol, benazepril, bupivacaine, buprenorphine, buspirone, carbinox-amine, chlordiazepoxide, clorazepate, dipsrridamole, fenfluramine, flecainide, metapra-mine, metipranolol, mexiletine, midazolam, naproxen, oxprenolol, phencyclidine, pipam-perone, pyrimethamine, thiopental, tianeptine, ticlopidine, trazodone, triprolidine, verapamil, vincristine, vindesine... 

The absorption of verapamil can be modestly reduced by antine-oplastic regimens containing cyclophosphamide, vincristine, and procarbazine, or vindesine, doxorubicin, cisplatin. 

A study in 9 patients with a variety of malignant diseases found that treatment with antineoplastics reduced the absorption of a single 160-mg oral dose of verapamil. The verapamil AUC in 8 patients was reduced by 40% (range 7 to 58%), and one patient conversely had a 26% increase. Five patients reeeived a modified COPP regimen (cyclophosphamide, vincristine, procarbazine, prednisone) and four received VAC (vindesine, doxornbicin, cisplatin). It is believed that these antineoplastics damage the lining of the upper part of the small intestine, which impairs the absorption of verapamil. The clinical relevance of this reduction does not appear to have been studied. Note that verapamil may affect levels of anthracyclines , (p.611), etoposide , (p.631), and possibly docetaxel , (p.662). In addition, nifedipine may affect the levels of vincristine , (p.671). 

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