Abstract
The antitumor activity of 4'-deoxyepivincristine (vinepidine, VNP) was examined against a human rhabdomyosarcoma line, HxRh12, grown as a xenograft in immune-deprived mice. The efficacy of VNP was lower than that of vincristine (VCR) but far superior to that of vinblastine (VLB) in this model. After i.p. administration, accumulation of [G- 3H]VNP in tumors was biphasic and progressive for at least 72 hr. In contrast, VCR and VLB achieved maximal tumor levels within 4 hr, after which the level of VCR was maintained but VLB levels decreased 3-fold by 72 hr. Analysis of tumor extracts by high performance liquid chromatography showed that at 72 hr after VNP injection 98% of the radiolabel chromatographed with parent compound. In normal tissues, VNP was cleared less rapidly than VCR or VLB, and analyses of tissue extracts suggested that VNP was less rapidly metabolized than VCR or VLB. This may account for why the potency of VNP is greater than that of VCR in mice.
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