New anti-inflammatory antedrugs: steroid acid esters and amides.

Therapeutic use of anti-inflammatory steroids is limited, due primarily to their suppressive effects on pituitary function and the immune system. In an attempt to circumvent the untoward systemic effects of corticosteroids, a new approach, the antedrug concept, was formulated by Lee. The term "antedrug" describes a drug that is active upon local application but is easily biotransformed, on entry into the systemic circulation, to an inactive or much less active metabolite. Thus, an antedrug acts only locally at the site of application and produces minimal systemic effects. This report provides a synopsis of the "evolution" of steroidal antedrugs, containing a metabolically labile carboxamide moiety, on the side-chain or at the C-16 position of prednisolone. Pharmacological screening of these steroidal antedrugs in the rat cotton pellet and croton oil-induced ear oedema bioassays led to the identification of P16CM, 11, as the lead compound and a viable drug candidate.