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 intravenous administration into the jugular and the hepatic portal veins, indicates extensive hepatic conjugation of phenol at low doses. However, 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 (less than 1 mg/kg), intestinal and hepatic conjugation are comparable. The capacity of the intestinal conjugating enzymes is remarkably high; at large doses (greater than 5 mg/kg), intestinal conjugation far exceeds the contribution of the hepatic and pulmonary enzymes.