Psychotropic drug metabolism in fetal alcohol syndrome.

Simultaneous intake of ethanol with chlorpromazine (thorazine), an antipsychotic drug, leads to about 60% decrease in the chlorpromazine removal from the rat blood. Studies with liver homogenates showed that ethanol inhibits the metabolism of this drug by about 50%. The inhibitory effect of ethanol on the metabolism of chlorpromazine can be largely abolished by pyrazole (2 mM) preincubation. Prolonged maternal ethanol consumption during pregnancy and lactation leads to a decrease in chlorpromazine metabolism in the fetal (30%), neonatal (46%) and maternal livers. Prolonged maternal ethanol intake also leads to an increase in the (UDPG)/(UDPGA) ratio in the suckling neonatal liver and the maternal liver. Simultaneous acute administration of ethanol (2g/kg) with psychotropic drugs such as chlordiazepoxide (librium), diazepam (valium), chlorpromazine (thorazine) or meprobamate (equanil) to pregnant or non-pregnant rats led to a decrease in the blood alcohol clearance rates. In another group of nonpsychotropic drugs tested, tolbutamide (orinase) produced the most pronounced (47%) decrease in blood alcohol clearance rates. This decrease was found to be accompanied by the inhibition of hepatic alcohol dehydrogenase.