Microbial models of drug metabolism: Microbial transformations of Trimegestone (R) (RU27987), a 3-keto-Delta(4,9(10))-19-norsteroid drug

Screening microorganisms for the biotransformation of the 3-keto-Delta(4.9( 10))-19-norsteroid RU27987 (Trimegestone(R)) resulted in the isolation of n ine identified metabolites, some of them being selectively produced by diff erent strains. Eight metabolites were found to be hydroxylated on various p ositions of the rings, and one was additionally epoxidized. These microbial metabolites could be used as chromatographic standards and two of them wer e found identical to the unknown major human metabolites, Moreover, most mi crobial metabolites were produced in sufficient amounts to be tested for th eir biological activities. All these features demonstrate the usefulness an d versatility of microbial biotransformation systems as a tool for early id entification and convenient production of potentially active mammalian and non-mammalian metabolites. (C) 1999 Elsevier Science Ltd. All rights reserv ed.