Effect of portacaval shunt on the disposition of drugs with and without first-pass effect

R Gugler, P Lain and DL Azarnoff

The pharmacokinetic parameters of lidocaine, antipyrine and salicylamide were studied in dogs before and after construction of a portacaval shunt. The systemic availability of antipyrine was not altered significantly by the surgical procedure whereas the availability of lidocaine and salicylamide, drugs with a marked first- pass effect, was increased from 14.8 +/- 2.8 to 81.3 +/- 5.2% and from 21.8 +/- 7.8 to 57.5 +/- 2.5%, respectively. Of the 78% first-pass extraction of salicylamide, 36% is due to hepatic extraction whereas the remaining 42% is accounted for by intestinal wall extraction. The presence of a portacaval shunt also reduced the plasma clearance of lidocaine and antipyrine, but not salicylamide. The apparent volume of distribution was decreased only with salicylamide. Surgical construction of a portacaval shunt in dogs in a good model to evaluate first-pass effect. Physicians should adjust downward the dose of drugs with a first-pass effect. Physicians should adjust downward the dose of drugs with a first-pass effect in patients with a surgical portacaval shunt or endogenous portal systemic shunts such as seen in cirrhosis of the liver.

Volume 195, Issue 3, pp. 416-423, 12/01/1975
Copyright © 1975 by American Society for Pharmacology and Experimental Therapeutics

This article has been cited by other articles:

				K. S. Pang MODELING OF INTESTINAL DRUG ABSORPTION: ROLES OF TRANSPORTERS AND METABOLIC ENZYMES (FOR THE GILLETTE REVIEW SERIES) Drug Metab. Dispos., December 1, 2003; 31(12): 1507 - 1519. [Full Text] [PDF]