SKF 525A displaces drugs from serum alpha 1-acid glycoprotein binding sites.
In vivo treatment of rats with beta-diethylaminoethyl-diphenylpropylacetate hydrochloride (SKF 525A), an inhibitor of hepatic monooxygenases, decreases the serum binding of oxprenolol and propranolol, which bind mainly to alpha 1-acid glycoprotein, but not that of phenytoin, which is bound to albumin. The effect was maximal 40 min after treatment and had disappeared after 6 hr, when enzyme inhibition was still present. A displacing effect was also observed when SKF 525A was added in vitro to serum of rats, dogs and humans and to human alpha 1-acid glycoprotein, whereas binding to human serum albumin was not affected. SKF 525A was found to be equipotent with tris(2-butoxyethyl)phosphate, a known displacer of binding of drugs from alpha 1-acid glycoprotein. When studying the pharmacokinetics or the effects of drugs after SKF 525A pretreatment, the possibility that altered protein binding may influence the findings should be considered.
D000633:Aminopyrine N-Demethylase / Q000378:metabolism; D000818:Animals; D004285:Dogs; D006801:Humans; D008099:Liver / Q000201:enzymology; D009961:Orosomucoid / Q000378:metabolism*; D010096:Oxprenolol / Q000097:blood*; D010672:Phenytoin / Q000097:blood*; D011335:Proadifen / Q000494:pharmacology*; D011433:Propranolol / Q000097:blood*; D011485:Protein Binding / Q000187:drug effects; D051381:Rats; D012709:Serum Albumin / Q000378:metabolism*
D009961:Orosomucoid; D012709:Serum Albumin; D010096:Oxprenolol; D010672:Phenytoin; D011433:Propranolol; D011335:Proadifen; D000633:Aminopyrine N-Demethylase