RT Journal Article
SR Electronic
T1 SKF 525A displaces drugs from serum alpha 1-acid glycoprotein binding sites.
JF Journal of Pharmacology and Experimental Therapeutics
JO J Pharmacol Exp Ther
FD American Society for Pharmacology and Experimental Therapeutics
SP 628
OP 630
VO 240
IS 2
A1 F M Belpaire
A1 B Chindavijak
A1 M G Bogaert
YR 1987
UL http://jpet.aspetjournals.org/content/240/2/628.abstract
AB 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.