The metabolism in animals and man of oxmetidine--a new histamine H2-receptor antagonist.

The absorption, distribution, metabolism and excretion of [14C]oxmetidine in rat, dog and man has been studied following both i.v. and oral administration. Excretion is rapid and essentially complete in all three species. The biliary route is predominant. Distribution of radioactivity is widespread although none is seen in the brain. Metabolite patterns in urine from rat, dog and man have been compared by thin-layer chromatography. Metabolite patterns in urine and bile from rat and dog have been compared by high pressure liquid chromatography. Six major metabolites have been isolated and identified including two O-glucuronides and one N-glucuronide.

Metabolism of the carbamate herbicide, asulam, in the rat.

The metabolism of [ring-14C]asulam, a systemic herbicide highly effective against bracken, has been studied in rats. Most of the radioactivity (76-100% dose) administered orally or intravenously is excreted in the urine in 24 h as unchanged asulam (61-74% dose), N4-acetylasulam (8-14%) and N4-acetylsulphanilamide (0.1-2.6%). Small amounts of radioactivity (0.3-7.4% dose) were present in the faeces, only traces (0.2-0.3%) were excreted in the bile, and no significant 14CO2 was detected. Perfusion of rat liver with 14C-asulam resulted in more extensive metabolism. Total amounts present in perfusate (81% total), bile (1%) plus liver (14%) were 23.1% for unchanged asulam, 25.7% for acetylasulam, less than 1% for acetylsulphanilamide, and 4.5% as conjugates of asulam and acetylasulam, together with several other unidentified metabolites. Asulam is acetylated more readily than sulphanilamide, by rat-liver homogenate, and the highest enzyme activity was associated with the mitochondrial fraction (2.4 pmol/mg protein per min). Although not hydroxylated by rats in vivo, evidence was obtained for the hydroxylation of asulam by rat-liver microsomal preparations in vitro.