STUDIES ON THE BIOLOGIC DISPOSITION OF METHOTRIMEPRAZINE

¹ Department of Pharmacology, University of California Medical Center, San Francisco, California

The absorption, distribution, excretion and metabolism of methotrimeprazine (Levoprome) were studied in the rat; an ultraviolet spectrophotometric procedure was used to measure the compound in biologic fluids. Methotrimeprazine was found to be well absorbed after oral administration, the half-life being 68 min. After absorption the compound left the blood rapidly and was taken up by various organs. Highest concentrations were found in the lungs and liver. Appreciable levels were found in the brain and kidneys and were still detectable 12 hr after drug administration. Somewhat lower drug concentrations were noted in muscle and fat. The pattern of distribution after intravenous administration of methotrimeprazine was similar to that after oral administration except that localization of the drug was greater in the brain and less in the liver. Less than 1% of the drug was recovered unchanged in the 24-hr urine of rats and humans. At least 10 metabolites of methotrimeprazine were found in urine, among which were five sulfoxides and five phenolic substances present either free or as glucuronide conjugates. Monodesmethyl methotrimeprazine sulfoxide was tentatively identified as one of the metabolites.