Nature 199, 498 - 499 (03 August 1963); doi:10.1038/199498a0

Experimental Production by 2-ethyl-2-phenyl Butyramide of Intrahepatic Cholestasis with Bile Plugs in Dogs

C. H. KEYSSER, J. A. WILLIAMS, L. E. VAN PETTEN & N. COY

Pathology Department, Squibb Institute for Medical Research, New Brunswick, New Jersey.

ORAL administration of 2-ethyl-2-phenyl butyramide in dogs produces intrahepatic cholestasis with bile plugs in bile canaliculi. Intrahepatic cholestasis with bile plugs is observed in a small percentage of patients receiving chlorpromazine, C-17 alkylated steroids, or several other chemically unrelated drugs. Histologically¹, this condition is characterized by bile plugs in bile canaliculi and deposition of bile pigment in liver and Kupffer cells. Changes in hepatic parenchymal cells, usually in the form of feathery degeneration and more rarely in the form of focal necrosis, are regarded as secondary to the biliary stasis. Infiltration of portal tracts was reported occasionally. Electron microscopic examination² of these livers showed dilation of some bile canaliculi and alteration in the microvilli of practically all; the microvilli were either absent or stunted and irregular in shape. Although functional³ as well as histochemical and ultrastructural⁴ changes were demonstrated in the livers of rats dosed with C-17 alkylated steroids, typical intrahepatic cholestasis with bile plugs has not been produced by a drug in normal animals¹.

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