Metabolism and excretion of the quaternary ammonium compound thiazinamium methylsulfate (Multergan) in man. I. Parenteral administration

Abstract

The quaternary ammonium compound thiazinamium was found to be metabolized by sulfoxidation solely. No ring hydroxylation products, nor demethylation products (e.g. promethazine) could be found. Thiazinamium sulfoxide was found both in urine and bile, but thiazinamium is-after parenteral administration - mainly excreted in the unchanged form. After intravenous injection about 40% of the dose was excreted, unchanged, in the urine. The excretion was very rapid and almost complete within eight hours. About 9% of the dose was excreted in the urine in the form of thiazinamium sulfoxide cations. After intramuscular injection virtually the same figures for urinary excretion were found. No correlation could be observed between urine production or pH and the amount of drug excreted in urine. In a study involving bile-fistula patients it was found that both thiazinamium cations and thiazinamium sulfoxide cations are excreted to a considerable extent in bile. The amount of unchanged drug in bile was almost equal to that in urine, but the amount of sulfoxide was slightly higher.