INVIVO CAPACITY OF HEPATIC AND EXTRAHEPATIC ENZYMES TO CONJUGATE PHENOL

  • 1 January 1984
    • journal article
    • research article
    • Vol. 12  (5) , 619-624
Abstract
Phenol has a high metabolic clearance in the rat and shows extensive first pass metabolism. The ability of the intestinal mucosa, liver and lung to conjugate phenol is investigated over a 35-fold dose range by employing a judicious choice of route of administration. Comparison of blood phenol concentration-time profiles, following i.v. administration into the jugular and the hepatic portal veins, indicates extensive hepatic conjugation of phenol at low doses. The capacity of the hepatic enzymes is readily saturated. This observation is confirmed in isolated perfused livers. Comparison of blood phenol concentration time profiles, following vascular administration into the carotid artery and the jugular vein, indicates substantial pulmonary conjugation of phenol. Although the extent of pulmonary conjugation is less than the hepatic contribution, it is evident over a wider dose range than the latter organ. Intestinal conjugation of phenol is assessed by comparison of data from intraduodenal and hepatic portal venous administration. At low doses of phenol (< 1 mg/kg), intestinal and hepatic conjugation are comparable. The capacity of the intestinal conjugating enzymes is remarkably high; at large doses (> 5 mg/kg), intestinal conjugation far exceeds the contribution of the hepatic and pulmonary enzymes. [Hepatic metabolism continues to be accepted as quantitatively the most important route of elimination for drugs and other xenobiotics. The role of extrahepatic biotransformation in the disposition and toxicity of foreign compounds is receiving increasing attention.].