Cefazolin serum protein binding and its inhibition by bilirubin, fatty acids and other drugs.

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Decroix MO, Zini R, Chaumeil JC, Tillement JP

Cefazolin serum protein binding and its inhibition by bilirubin, fatty acids and other drugs.

Biochem Pharmacol. 1988 Jul 15;37(14):2807-14.

PubMed ID

3395358 [ View in PubMed

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Abstract

This paper describes the protein binding of cefazolin to human serum and to human serum albumin (HSA) using equilibrium dialysis. The drug is exclusively bound to HSA with a moderate affinity, Ka = 16,600 +/- 1600 M-1, and one saturable binding site, n = 0.73 +/- 0.02. Moreover cefazolin shows a dose-dependent binding leading a possible increase of the free fraction (when its total concentration increases). This antibiotic is displaced by free fatty acids (FFA) and bilirubin. Cefazolin binding to human serum and human serum albumin (HSA) was studied in presence of acidic drugs. At low concentrations clofibric acid and phenylbutazone both exhibiting high affinity for HSA displace strongly cefazolin. Valproic and salicylic acids, sulfamethoxazole, cefoperazone which have approximately the same affinity as cefazolin, must be used at higher concentrations to displace this antibiotic. A particular phenomenon was observed with cefazolin on HSA when associated with furosemide. A low concentration (5-25 microM) of this drug induces a positive cooperativity of binding between cefazolin and HSA. But at a molar ratio of furosemide to albumin greater than one, such cooperative interaction disappears and a competitive inhibition of cefazolin binding occurs. For all drugs studied, a competitive inhibition was found except for tryptophan. Finally, it is concluded that cefazolin shares the warfarin binding site on HSA.

DrugBank Data that Cites this Article

Drug Carriers

Drug	Carrier	Kind	Organism	Pharmacological Action	Actions
Cefazolin	Serum albumin	Protein	Humans	Unknown	Other/unknown	Details