ON THE SPECIFICITY OF PENULTIMATE OXIDATION

THE FATE OF 5-ETHYL-5-n-HEXYLBARBITURIC ACID

¹ Department of Pharmacology and Experimental Therapeutics, The Johns Hopkins University School of Medicine, Baltimore, Maryland

The fate of 5-ethyl-5-n-hexylbarbituric acid (hexethal, Ortal) was studied in dogs given the drug in a variety of ways. Ten ether-extractable metabolites accounting for 48 to 58% of the dose were isolated by countercurrent fractionation. The -1 alcohol amounted to 15%, and the -1 ketone, to 9% of the dose. The neutral fraction included 3 other alcohols (4.5% of the dose), 1 other ketone (2%) and a compound (0.6%) which upon acid hydrolysis yielded an unknown dialkylbarbiturate containing a carboxylic acid group. The acidic metabolite fraction was composed of the -oxidation product (4%), a hydroxy acid (2%) and the -oxidation product (16%). Glucuronic acid conjugates of the alcoholic metabolites were present only in small quantities (1% of the dose).

The present findings prove that oxidation is not restricted to the and -1 carbon atoms of dialkylbarbiturates. However, these 2 atoms appear to bear the brunt of the oxidative attack.