THE PATHWAYS OF PROPRANOLOL METABOLISM IN DOG AND RAT LIVER 1O,000g SUPERNATANT FRACTIONS

By use of an XAD-2 sample purification procedure, the quantitative patterns of the In vitro metabolism of propranolol and four of its metabolites have been examined by a GC/MS/DATA procedure. Supematant fractions (10,000g) from both dog and rat livers have been used to degrade propranolol, 4-hydroxypropranolol, N-deiso-propylpropranolol, propranolol glycol, and a-naphthoxylactlc acid. There were both qualitative and quantitative differences in dog and rat metabolism; rat 10,000g supernatant fraction produced more hydroxylation than that of the dog. a-Naphthol is not produced from propranolol directly, but rather from a-naphthoxylactic acid with an Intermediate step requiring NAD as a cofactor. We observed no degradation of 4-hydroxypropranolol from the 10,000g supernatant preparations. Thus, 1,4-naphthalenediol is more likely a product of 4-hydroxypropranolol glycol. The metabolism of propranolol is an important determinant o