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Severe INR elevation in a patient with choledocholithiasis receiving cefoperazone
Hakan Alagozlu1, Mehmet Cindoruk, Selahattin Unal
1Department of Internal Medicine, Division of Gastroenterology, Medical Faculty of Gazi University, Ankara, Turkey. hakanalagoz@gazi.edu.tr
Clinical Drug Investigation
|December 14, 2006
Summary
Cefoperazone, an antibiotic, can prolong prothrombin time and INR by interfering with vitamin K metabolism. This case highlights a potential link between cefoperazone and choledocholithiasis due to these effects.
Area of Science:
- Pharmacology
- Hepatology
- Gastroenterology
Background:
- Cefoperazone is a third-generation cephalosporin antibiotic.
- It possesses an N-methyl-thiotetrazole (NMTT) side chain.
- This side chain is known to inhibit vitamin K-dependent carboxylation.
Observation:
- NMTT-containing cephalosporins can alter hepatic glutathione redox state.
- This leads to increased oxidised glutathione, inhibiting vitamin K epoxide reduction.
- Cefoperazone is not metabolized and is primarily excreted via bile.
Findings:
- Hepatic impairment significantly reduces cefoperazone clearance and prolongs its half-life.
- A case of choledocholithiasis is presented.
- This condition was associated with prolonged prothrombin time and INR.
Implications:
- Cefoperazone therapy may contribute to vitamin K deficiency-related coagulopathy.
- Clinicians should monitor prothrombin time and INR in patients receiving cefoperazone, especially those with hepatic impairment.
- This highlights a potential iatrogenic cause for biliary complications.
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