The pathways of propranolol metabolism in dog and rat liver 10,000g 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. Supernatant fractions (10,000g) from both dog and rat livers have been used to degrade propranolol, 4-hydroxypropranolol, N-deisopropylpropranolol, propranolol glycol, and alpha-naphthoxylactic 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. alpha-Naphthol is not produced from propranolol directly, but rather from alpha-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.