Pharmacokinetics-activity relationships of a new non-hormonal antifertility agent: 3-(2-ethylphenyl)-5-(3-methoxyphenyl)-1H-1, 2,4-triazole, in the rat and the hamster.

The pharmacokinetic profiles of a new non-hormonal anti-fertility agent, DL 111-IT, were studied in rats and hamsters given the 14C labelled compound parenterally dissolved in aqueous or oily vehicles. In both species, DL 111-It was rapidly metabolized and excreted when given intravenously or subcutaneously in aqueous vehicles (half-lives = 15-45 min.), whereas the kinetics were prolonged when it was administered in oily formulations (half-lives = 7-10 h). Binding studies revealed a high affinity of DL 111-IT for rat serum albumin (Ka = 6 X 10(5) 1/mole). The radioactivity concentrations in different tissues of pregnant rats appeared to be uniform with the excretory organs and lungs being the main target tissues. At the site of action, the utero-placental complex, the levels of total 14C were comparable to those in plasma, whereas the concentration of unchanged DL 111-IT was higher and remained so for a longer time. A comparison between the kinetic profiles and the activity data after single or multiple dose administration in different formulations, clearly indicates a close relationship between activity and plasma and tissue (utero-embryo placental complex) levels of DL 111-IT, and also makes clear the influence of the formulation and of the treatment schedule on the anti-fertility activity of the compound.