Species variation in the metabolism of a substituted cinnamate ester anti-inflammatory pro-drug

Abstract

1. The metabolic fate of the substituted cinnamic acid ester, Ro 03–6037, has been examined in rat, mouse, baboon, dog, marmoset, rabbit and man.

2. All species are capable of reducing the cinnamate double bond, but the subsequent one-carbon fragment loss can be carried out only by rat, dog, rabbit and marmoset.

3. The inability of man, as well as baboon and mouse, to perform this terminal metabolic step, which results in formation of the active anti-inflammatory agent, renders the compound unsuitable as a drug for humans.

4. Reduction of the double bond is not carried out by gut flora.

5. An h.p.l.c. analytical method is described for estimation of the metabolites in biological fluids.