Harrison L M, Fennessey P V
Department of Pediatrics, University of Colorado Health Sciences Center, Denver 80262.
J Steroid Biochem. 1990 Aug 14;36(5):407-14. doi: 10.1016/0022-4731(90)90081-3.
Methandrostenolone dose (amount and duration) and methods of isolation from urine can influence the identification and quantitation of methandrostenolone metabolites. Long-term use of methandrostenolone at high dosages led to the appearance of unmetabolized drug in the urine and contributed to the identification of a previously unreported metabolite, 3 beta, 6 section, 17 beta-trihydroxy-17 alpha-methyl-5 section-1-androstene. Exposure of methandrostenolone in vitro to acid conditions induced a retropinacol rearrangement in the D-ring of the methandrostenolone molecule, causing the formation of 18-nor-17,17-dimethyl-1,4,13(14)-androstatrien-3-one in large amounts. The same acidic conditions led to the addition of a hydroxyl at the 6 position of the B-ring of either the retropinacol rearrangement products or native methandrostenolone resulting in the formation of 6 beta-hydroxy-18-nor-17,17-dimethyl-1,4,13(14)-androstatrien-3-one, 6 alpha- hydroxy-18-nor-17,17-dimethyl-1,4,13(14)-androstatrien, 6 beta-17 alpha-methyl-1,4-androstadien-3-one and 6 alpha,17 beta-dihydroxy-17 alpha-methyl-1,4-androstadien-3-one. Hydroxylation of native methandrostenolone at the 6 position also occurs endogenously. However, no evidence of an endogenous retropinacol rearrangement was found. Silylating agents alone can induce the formation of small amounts of 6 beta-17 beta-dihydroxy-17 alpha-methyl-1,4-androstadien-3-one. Discrepancies between previously published reports on methandrostenolone metabolism in man are discussed and compared with an animal model.
甲基雄烯醇酮的剂量（数量和持续时间）以及从尿液中分离的方法会影响甲基雄烯醇酮代谢物的鉴定和定量。长期高剂量使用甲基雄烯醇酮会导致尿液中出现未代谢的药物，并有助于鉴定一种先前未报告的代谢物，即3β,6β,17β - 三羟基 - 17α - 甲基 - 5β - 1 - 雄烯。甲基雄烯醇酮在体外暴露于酸性条件下会在其分子的D环中引发频哪醇重排，导致大量生成18 - 去甲 - 17,17 - 二甲基 - 1,4,13(14) - 雄甾三烯 - 3 - 酮。相同的酸性条件会导致在频哪醇重排产物或天然甲基雄烯醇酮的B环的6位添加一个羟基，从而生成6β - 羟基 - 18 - 去甲 - 17,17 - 二甲基 - 1,4,13(14) - 雄甾三烯 - 3 - 酮、6α - 羟基 - 18 - 去甲 - 17,17 - 二甲基 - 1,4,13(14) - 雄甾三烯、6β - 17α - 甲基 - 1,4 - 雄二烯 - 3 - 酮和6α,17β - 二羟基 - 17α - 甲基 - 1,4 - 雄二烯 - 3 - 酮。天然甲基雄烯醇酮在6位的羟基化也会内源性发生。然而，未发现内源性频哪醇重排的证据。单独的硅烷化剂可诱导生成少量的6β,17β - 二羟基 - 17α - 甲基 - 1,4 - 雄二烯 - 3 - 酮。讨论了先前发表的关于人体中甲基雄烯醇酮代谢的报告之间的差异，并与动物模型进行了比较。
