Effect of cyclodextrins on protein binding of drugs: the diflunisal/hydroxypropyl-beta-cyclodextrin model case.
The binding of diflunisal to hydroxypropyl-beta-cyclodextrin (HP beta CD), bovine serum albumin (BSA), human serum albumin (HSA), normal human plasma, and mixed solutions of HP beta CD/protein was studied at 25 degrees C, pH 7.4, by potentiometry using an electrode selective to diflunisal. The experimental data for diflunisal/HP beta CD fit well to the 1:1 binding model. The binding of diflunisal with each of the studied proteins was compatible with a model having two independent classes of binding sites. The binding of diflunisal in mixed solutions HP beta CD/BSA, HP beta CD/HSA, and HP beta CD/plasma increased considerably when the HP beta CD concentration was increased. The binding behavior of the two biomolecules in the mixed solutions of HP beta CD/BSA or HP beta CD/HSA was described with an "additive" model formulated on the basis of the estimates of the binding parameters of diflunisal derived from the separate experiments with each one of the binders tested. The lower than theoretical binding observed in HP beta CD/plasma solutions was ascribed to the competitive displacement of diflunisal from the HP beta CD cavity by plasma cholesterol.
Sideris
E E
EE
Department of Pharmacy, University of Athens, Greece.
Koupparis
M A
MA
Macheras
P E
PE
D000073738:2-Hydroxypropyl-beta-cyclodextrin; D000818:Animals; D002417:Cattle; D003505:Cyclodextrins / Q000494:pharmacology*; D004061:Diflunisal / Q000097:blood / Q000493:pharmacokinetics*; D004566:Electrodes; D006801:Humans; D007202:Indicators and Reagents; D008954:Models, Biological; D011143:Polyvinyl Chloride; D011199:Potentiometry; D011485:Protein Binding / Q000187:drug effects; D012709:Serum Albumin / Q000378:metabolism; D012710:Serum Albumin, Bovine / Q000378:metabolism; D047392:beta-Cyclodextrins
D003505:Cyclodextrins; D007202:Indicators and Reagents; D012709:Serum Albumin; D047392:beta-Cyclodextrins; D000073738:2-Hydroxypropyl-beta-cyclodextrin; D012710:Serum Albumin, Bovine; D004061:Diflunisal; D011143:Polyvinyl Chloride