A high-performance liquid chromatographic procedure utilizing u.v. and radioactivity detection was employed to examine the metabolism of the epipodophyllotoxin derivative VP 16-213 by the rat in vivo and in liver extracts and subcellular fractions. VP 16-213 has been shown to be metabolized extensively by rat liver homogenates and rat liver microsomes, with the formation of one major metabolite. The metabolite formed in vitro was the only metabolite present in plasma samples of rats treated with i.p. injections of VP 16-213. Based on its chromatographic and solubility characteristics, the metabolite is probably a cis- or trans-hydroxy acid derivative. The liver is involved in the metabolism of VP 16-213, and the localization of the enzyme(s) responsible for the formation of the major metabolite is in the microsomal fraction.
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