Metabolism of ³⁶Cl-ornidazole after oral application to the male rat in relation to its antifertility activity

Abstract

1. The antimycotic ornidazole (a male antifertility agent in rats) was synthesized incorporating ³⁶Cl in the chloropropyl sidechain and its metabolism was investigatedin the male rat after oral ingestion. 2. Blood levels of radioactivity were low over the first 24 h and there was no tissue accumulation of radioactivity over 48 h. 3. Most of the excreted radioactivity (20% of the ingested dose) appeared in the urine within the first 24 h. 4. Three major compounds were detected in 0-24-h urine samples and were characterized as ornidazole (13% of total radioactivity), Cl⁻ (22%) and 3-chlorolactate (30%), the oxidation product of 3-chlorolactaldehyde. 5. No polyuria or glucosuria was observed following the oral administration of ornidazole,suggestingthat any (R)-3-chlorolactate producedwas insufficient toaffect renal metabolism. 6. Conversion of ornidazole initially to (R,S)-α-chlorohydrin or ultimately to the glycolytic inhibitor (S)-3-chlorolactaldehyde could explain its antifertility action in the male rat.