Effect of portacaval shunt on the disposition of drugs with and without first-pass effect.
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.
D000818:Animals; D000983:Antipyrine / Q000378:metabolism*; D001682:Biological Availability; D004285:Dogs; D005260:Female; D006207:Half-Life; D007700:Kinetics; D008012:Lidocaine / Q000378:metabolism*; D008099:Liver / Q000378:metabolism; D008297:Male; D011167:Portacaval Shunt, Surgical; D012457:Salicylamides / Q000378:metabolism*; D013997:Time Factors
D012457:Salicylamides; D008012:Lidocaine; D000983:Antipyrine