Effect of hepatic cytosol on postnatal drug metabolism.

Postnatal maturation for indomethacin O-demethylation in freshly isolated hepatocytes and 10,000 g liver homogenates of rabbit was found to be significantly different from that observed in rabbit hepatic microsomes. Addition of hepatic cytosol (100,000 g supernatant) from day 10 postnatal rabbits significantly inhibited indomethacin O-demethylation by hepatic microsomes from adult rabbits. Kinetic studies demonstrated that the inhibition was competitive and consistent with the concentration of cytosol. The pattern of postnatal maturation for hepatic microsomal drug metabolism may in part be related to changes in the concentration of endogenous cytosolic inhibitors.