Fate of the anthelmintic, phenothiazine, in man

Abstract

1. Radiolabelled [35 S]-phenothiazine has been administered orally to two healthy adult male volunteers (6mg kg -1 body weight). Faeces were the major route of excretion of radioactivity (68%), the remainder being eliminated via the urine (32%) with an estimated urinary half-life (biphasic) of 6-16 h. Over the 5 days of the study a complete recovery of radioactivity was achieved. 2. From urinary data, it was shown that metabolism occurred via ring carbon oxidation to form phenothiazone and thionol and via ring sulphur oxidation to form phenothiazine sulphoxide. The majority of urinary material (92%) was present in the form of conjugates of phenothiazine and phenothiazone. Only unchanged phenothiazine was detected in the faeces. Phenothiazine sulphoxide was reduced to phenothiazine during incubation with faecal homogenates.