Amphetamine metabolism in mice exposed chronically to phenobarbital and to phenobarbital with carbon tetrachloride.

The metabolism of amphetamine was studied in three groups of mice, including normal mice (N), mice given chronic doses of phenobarbital via their drinking water (PB), and mice exposed to carbon tetrachloride vapors daily during the course of chronic phenobarbital consumption (PB/CCl4). Renal and hepatic tissue from animals of each group were examined by electron microscopy. Mice in the PB/CCl4 group demonstrated the classical symptoms of carbon tetrachloride-induced hepatic cirrhosis, and structural damage to the kidney. The PB group presented a normal renal pathology, but ultrastructural changes including swollen mitochondria and dilation of the endoplasmic reticulum were evident in the hepatocytes. The N, PB and PB/CCl4 mice excreted 84.5, 61.5 and 72.3 percent respectively of a dose of 14C-amphetamine sulfate in the 0-72 hour urine. Seven major urinary metabolites were detected in the normal group, 4 in PB group, and 3 in the PB/CCl4 group. Unchanged amphetamine, rho-hydroxyamphetamine and benzoic acid were tentatively identified by combined techniques of gas chromatography and thin-layer chromatography with autoradiography.