Studies on the enzymatic cleavage of norethisterone oenanthate

Norethisterone oenanthate (NET OEN) was extensively hydrolysed in rabbit, rat and guinea pig plasma (99.9%, 76.1% and 46.0% hydrolysed in 90 min, respectively). In contrast, there was negligible hydrolysis (less than 2.5%) in dog, goat and human plasma. Rabbit liver, kidney, gut wall, stomach, heart and muscle showed marked hydrolytic activity in vitro, but there was little hydrolysis of NET OEN by either human muscle or fat. It is proposed that following intramuscular administration of NET OEN to rabbits, the ester is rapidly hydrolysed at the injection site and in the circulation whereas in humans the liver is the main site of hydrolysis since neither muscle nor plasma cause significant breakdown of the ester. The rabbit is not a good model for predicting the pharmacokinetics of NET OEN in humans.