Glyburide-Induced Hepatitis

Abstract

Drug-induced hepatotoxicity, although common, has been reported only infrequently with sulfonylureas. For glyburide, a second-generation sulfonylurea, only two brief reports of hepatotoxicity exist. Two patients with type II diabetes mellitus developed an acute hepatitis-like syndrome soon after initiation of glyburide therapy. There was no serologic evidence of viral infection, and a liver biopsy sample showed a histologic pattern consistent with drug-induced hepatitis. Both patients recovered quickly after stopping glyburide therapy and have remained well for a follow-up period of 1 year. Glyburide can produce an acute hepatitis-like illness in some persons.

Use ofin vitrotransporter assays to understand hepatic and renal disposition of new drug candidates

“…• molecular weight > 500 for humans (> 250 for rat), as compounds of this size are more likely to be eliminated by the hepato-biliary pathway [190] • log D pH 7.4 > 0, as hydrophobic compounds pass through cell membranes such as the liver, where CL H is an effective means of removal from the body [191] • liver/plasma ratio > 1, as this implies hepatic uptake • literature or historical data indicating role of hepatic clearance for chemical class, for example, the thiazolidinediones, endothelin A receptor antagonists and statin drugs [49,[192][193][194][195][196][197] • evidence of hepatic toxicity in chemical class, for example, troglitazone [68,197,198], bosentan [199], glyburide [200], and tacrine [201] • predicted human biliary excretion > 50%…”

Mechanistic Modeling Reveals the Critical Knowledge Gaps in Bile Acid–Mediated DILI

“…1 Furthermore, known inhibitors of BSEP and other bile acid (BA) transporters have been implicated in the case studies of DILI. Glibenclamide has been associated with lobular liver injury in the clinic, 2,3 bosentan has been associated with many cases of hepatotoxicity and carries a black-box warning for hepatotoxicity, 4 and troglitazone was withdrawn from the market due to idiosyncratic DILI. 5,6 Currently marketed BSEP inhibitors, such as lapatinib, have been given black-box warnings due to issues with liver toxicity.…”

Glipizide treatment with short-term alcohol abuse resulting in subfulminant hepatic failure

“…The liver demonstrated cholestasis, bile-duct proliferation, and panacinar necrosis consistent with a hypersensitivity drug reaction. Similar cases of non-fatal hepatitis consistent with a hypersensitivity reaction have been reported with glyburide [3] and gliclazide [4]. In all four cases, liver enzymes were only moderately elevated and only the patient treated with glipizide manifested hepatic failure.…”