Phenytoin as a possible cause of acetaminophen hepatotoxicity: case report and review of the literature.
A 55-year-old woman was hospitalized for treatment of community-acquired pneumonia. Unexplained, moderate elevations in hepatic transaminase and enzyme levels prompted review of her drug regimen. She had taken acetaminophen 1,300-6,200 mg/day during the hospitalization. She also received phenytoin for posttraumatic seizures. Acetaminophen was discontinued, and the patient's liver chemistries returned to normal within 2 weeks of discharge. Acetaminophen is metabolized in part by cytochrome P450 (CYP) 2E1, and inducers of CYP2E1 are known to predispose patients to acetaminophen-related hepatotoxicity. Phenytoin induces CYP2C and CYP3A4 isoforms, but not CYP2E1. The literature suggests, however, that CYP3A4 may participate in acetaminophen metabolism to a greater extent than previously realized, and induction of this isoform may predispose patients to acetaminophen-induced hepatotoxicity.
Brackett
C C
CC
Division of Pharmacy Practice and Administration, College of Pharmacy, The Ohio State University, Columbus 43210, USA.
Bloch
J D
JD
D000082:Acetaminophen / Q000009:adverse effects*; D018712:Analgesics, Non-Narcotic / Q000009:adverse effects*; D000927:Anticonvulsants / Q000009:adverse effects*; D019392:Cytochrome P-450 CYP2E1 / Q000096:biosynthesis / Q000378:metabolism; D051544:Cytochrome P-450 CYP3A; D003577:Cytochrome P-450 Enzyme System / Q000096:biosynthesis / Q000378:metabolism; D005260:Female; D006801:Humans; D008111:Liver Function Tests; D008173:Lung Diseases, Obstructive / Q000150:complications; D008875:Middle Aged; D006899:Mixed Function Oxygenases / Q000096:biosynthesis / Q000378:metabolism; D010672:Phenytoin / Q000009:adverse effects*; D012640:Seizures / Q000150:complications / Q000188:drug therapy; D020246:Venous Thrombosis / Q000150:complications
D018712:Analgesics, Non-Narcotic; D000927:Anticonvulsants; D000082:Acetaminophen; D010672:Phenytoin; D003577:Cytochrome P-450 Enzyme System; D006899:Mixed Function Oxygenases; D019392:Cytochrome P-450 CYP2E1; C104464:CYP3A protein, human; D051544:Cytochrome P-450 CYP3A; C510163:CYP3A4 protein, human