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Clinical Drug Investigation 2006

Severe INR elevation in a patient with choledocholithiasis receiving cefoperazone.

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Hakan Alagozlu
Mehmet Cindoruk
Selahattin Unal

Keywords

Abstract

Cefoperazone is a third-generation cefalosporin that contains the N-methyl- thio-tetrazole (NMTT) side chain, which inhibits vitamin K-dependent carboxylation. Administration of NMTT-containing cefalosporins can cause alterations in the hepatic glutathione redox state, resulting in a dose-related increase in oxidised glutathione, which is responsible for the inhibition of microsomal reduction of vitamin K epoxide. In addition, cefoperazone is not metabolised and is excreted predominantly through the bile. In patients with hepatic impairment, the clearance of cefoperazone has been shown to be significantly reduced and the half-life prolonged. We report a case of choledocholithiasis related to a prolonged prothrombin time and INR secondary to cefoperazone therapy.

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