Biotransformation of lofexidine in humans.
1. Concentrations of unchanged drug and patterns of radioactive components in urine have been determined by h.p.l.c. following single oral doses of [14C]lofexidine hydrochloride (0.32 mg) to six human subjects. 2. A mean of 12% of the administered dose was excreted in urine as unchanged lofexidine, but the wide range (5-20% dose) indicated significant intersubject variation in the extent of biotransformation. This drug would appear to be metabolized more extensively than the related anti-hypertensive agent, clonidine. 3. The principal metabolite of lofexidine was 2,6-dichlorophenol, which was apparently excreted in urine as two O-glucuronic acid conjugates. The same two metabolites were also the main 14C components circulating in plasma at peak 14C concn. Formation of the phenol from lofexidine probably involved direct O-dealkylation rather than stepwise degradation of the side-chain. 4. Patterns of 3H components in the urine of rats and dogs after oral administration of [3H]lofexidine hydrochloride (0.1 mg/kg) were generally similar to those in human urine.
D000328:Adult; D001711:Biotransformation; D002851:Chromatography, High Pressure Liquid; D003000:Clonidine / Q000031:analogs & derivatives* / Q000097:blood / Q000378:metabolism / Q000652:urine; D004305:Dose-Response Relationship, Drug; D006801:Humans; D006868:Hydrolysis; D008297:Male; D013058:Mass Spectrometry
D003000:Clonidine; C025655:lofexidine