Metabolism of proxyphylline in man. Isolation and identification of metabolites in urine.

The urinary excretion of radioactivity has been measured in man following intravenous injection of 400 mg of [8-14C]proxyphylline. Of the radioactive dose, 95% was recovered in urine 3 days after drug administration. Proxyphylline metabolites were isolated from the urine excreted between 8 and 19.5 hr after drug administration and separated into four different fractions. Unmetabolized proxyphylline accounted for 22% of the excreted radioactivity. The main metabolite was identified as 1-methyl-7-(beta-hydroxypropyl)xanthine, which accounted for 60--65% of the excreted radioactivity. About 1% was excreted as the corresponding 1-methyl-7-(beta-hydroxypropyl)uric acid. Nine percent of the dose was excreted as glucuronic acid conjugates, mainly as proxyphylline glucuronide, but 0.5--1% of 1-methyl-7-(beta-hydroxypropyl)xanthine glucuronide, was also found. The previously postulated metabolite, theophylline, was not excreted in detectable amounts.