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Interaction of mixed micelles formed from glycocholic acid and lecithin with the protein binding of various drugs.
Author(s) -
Guentert TW,
Oie S,
Paalzow L,
Frey BM,
Brandt R,
Aarons LJ,
Rowland M
Publication year - 1987
Publication title -
british journal of clinical pharmacology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.216
H-Index - 146
eISSN - 1365-2125
pISSN - 0306-5251
DOI - 10.1111/j.1365-2125.1987.tb03093.x
Subject(s) - glycocholic acid , lecithin , micelle , chemistry , plasma protein binding , pharmacology , biochemistry , medicine , cholesterol , organic chemistry , aqueous solution , cholic acid
Mixed micelles (MM) formed from glycocholic acid and lecithin are suited to solubilize lipophilic drugs for intravenous use. To test for possible drug‐drug interactions, the protein binding of a series of agents known to bind to different sites on albumin (diazepam, warfarin, ketoprofen, frusemide, probenecid) and additionally (prazosin, quinidine, propranolol) or exclusively (disopyramide) to alpha 1‐acid glycoprotein or to transcortin (prednisolone) was determined in the presence and absence of MM. Concentrations of MM, corresponding to the maximum possible plasma concentration achieved by injecting the highest clinical doses of MM into the systemic circulation, had little or no effect on the unbound fractions of drugs known to bind exclusively to albumin. Only at five times higher MM concentrations were the free fractions substantially increased (by up to 45%). Unbound fractions of drugs bound with high affinity but low capacity to alpha 1‐acid glycoprotein were increased between 50‐85% even at ‘therapeutic’ doses of MM. The present study suggests that drugs solubilized by MM should be given by slow injection or infusion to patients already receiving drugs which are highly bound to alpha 1‐acid glycoprotein.