In vitro hydroxylation of the synthetic gestagen, norgestrel

The in vitro metabolism of stereo-isomers (D, L and the racemic mixture DL) of norgestrel by a microsomal fraction from rabbit liver was investigated. The metabolism of the biologically active D-norgestrel was more rapid than that of L-norgestrel which is biologically inactive. This was mainly due to the more ready conversion of D-norgestrel to ring-A reduced metabolites. There was no difference between the two isomers in respect of the amount undergoing hydroxylation; about 40% of each isomer was converted to hydroxylated metabolites after 30 min incubation. However, there were differences between the isomers, D-norgestrel being converted mainly to the 16 beta-hydroxysteroid and L-norgestrel to the 16 alpha-hydroxysteroid. Similar amounts of both isomers were hydroxylated at C-6. The metabolism of the racemic mixture was intermediate between that of the D and L isomers.