Related Experiment Video
Updated: Aug 4, 2026

Technique of Porcine Liver Procurement and Orthotopic Transplantation using an Active Porto-Caval Shunt
Published on: May 7, 2015
Nonlinear formation of propranolol metabolites in dogs after portacaval transpositions
Abstract:
The formation of four major metabolites of propranolol by the liver was examined at steady state in three dogs that had undergone surgical portacaval transposition, following which injection of drug into the hindlimb delivers the total dose to the liver. Propranolol was infused directly into the liver via a hindlimb vein at dose rates ranging from 1.01 to 6.3 mg/min. In all dogs the formation of 4-hydroxypropranolol, alpha-naphthoxylactic acid, and propranolol glycol was saturable. Vmax and Km values were determined at steady state by relating the rate of excretion of each metabolite into bile and urine to the blood concentration of propranolol. The formation of propranolol glucuronide was a first order process. The use of a dog with a portacaval transposition has permitted development of a method to estimate, in vivo, the kinetic properties of enzymes responsible for hepatic first-pass metabolism of drugs.
Related Concept Videos
Drug Biotransformation: Overview
Drug Biotransformation: Overview
Hepatic Drug Excretion: Enterohepatic Cycling
Post-release drugs and metabolites can be reabsorbed into the body from the intestine. For conjugated metabolites like glucuronides, reabsorption requires enzymatic hydrolysis by intestinal microflora. This...
Nonlinear Pharmacokinetics: Causes of Nonlinearity
Nonlinear drug absorption can occur when the process is rate-limited by solubility, carrier-mediated transport systems, or saturation of the presystemic gut wall or hepatic metabolism. For instance, high doses of riboflavin...
Nonlinear Pharmacokinetics: Dependence of Elimination Half-Life and Dose Clearance
A study on guinea pigs examined the...
Drug Accumulation During Multiple Dosing: Intermittent IV Infusions

