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.
D000818:Animals; D004285:Dogs; D005260:Female; D008297:Male; D008862:Microsomes, Liver / Q000378:metabolism*; D009249:NADP; D009284:Naphthols / Q000378:metabolism; D009536:Niacinamide; D011433:Propranolol / Q000031:analogs & derivatives / Q000378:metabolism*; D051381:Rats; D013347:Subcellular Fractions / Q000378:metabolism
D009284:Naphthols; C012878:N-desisopropylpropranolol; C001422:4-hydroxypropranolol; D009536:Niacinamide; D009249:NADP; D011433:Propranolol