Effect of pressure on oxidative metabolism of drugs by mouse hepatic microsomes.

The metabolism of antipyrene and delta-9-tetrahydrocannabinol (delta-9-THC) was studied in vitro with mouse liver supernatant and 105,000 g microsomes at 450 atm pressure. No significant change in rate of antipyrene metabolism was detected, whereas a slight (5.6%) but nonsignificant reduction in the rate of metabolism of delta-9-THC was found. Pressure did, however, produce a significant (23%) reduction in the formation of the 11-hydroxy metabolite from delta-9-THC, but at the same time had no effect on the production of the other major metabolite, 8-alpha-hydroxy-delta-9-THC. This is possibly due to a differential effect on cytochrome P-450 isozymes. Mechanisms for the possible cause of the inhibition of metabolism are discussed.