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Gastroenterology. 1979 Jul;77(1):96-102.

Enhanced bioavailability and decreased clearance of analgesics in patients with cirrhosis.


The effect of moderate cirrhosis on the bioavailability and systemic clearance of three model analgesic compounds (pethidine, pentazocine, and salicylamide) with substantial first-pass metabolism was examined in 8 cirrhotic subjects and 4 agematched healthy controls. There was a 46% decrease in the clearance of pentazocine and a 278% increase in bioavailability. The corresponding figures for pethidine were 36% and 81%. The area under the plasma curve after oral salicylamide was increased by 551% in cirrhotic subjects compared with controls. This study demonstrated that drugs with the highest hepatic clearance will have the largest relative increases in bioavailability in cirrhotic patients due to portosystemic shunting. The decrease in clearance and increase in bioavailability will have multiplicative, rather than simply additive, effects on total area under the curve and, if related, pharmacologic response.

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