Decreased hepatic vitamin A after drug administration in men and in rats

Eleven patients with moderate drug-induced liver changes were found to have extremely low hepatic vitamin A levels (less than 10% of normal). Their serum vitamin A, retinol-binding protein, and transthyretin were only slightly affected. In rats, two representative drugs (phenobarbital and methylcholanthrene) produced a significant depression of hepatic vitamin A, whereas plasma vitamin A levels remained normal. The livers of drug-treated animals showed no abnormalities except for the expected proliferation of the smooth endoplasmic reticulum and induction of microsomal enzymes and cytochrome P-450 (phenobarbital) and P-448 (methylcholanthrene). These findings suggest that the decrease in hepatic vitamin A may be secondary, at least in part, to enhanced microsomal metabolism.