Ethanol and psychotropic drug interaction during pregnancy and lactation.
Prolonged maternal ethanol consumption for 8 days during pregnancy or for five days immediately after birth resulted in 30-46 per cent inhibition in the rate of chlorpromazine metabolism by the rat fetal and neonatal livers respectively. A significant increase in hepatic NADH/NAD and UDPG/UDPGA ratios was observed in suckling neonatal and maternal livers from the ethanol-fed group. Acute administration of ethanol with chlorpromazine led to about 60 per cent inhibition of the metabolism of chlorpromazine. This inhibitory effect of ethanol on the metabolism of chlorpromazine was largely abolished by preincubation of liver homogenates with pyrazole (2 mM). Lactate (10 mM) addition to liver homogenates resulted in a significant inhibition of chlorpromazine metabolism. It is suggested that maternal ethanol consumption during preganancy and lactation inhibits the hepatic metabolism of drugs such as chlorpromazine which require glucuronidation for their detoxification. This ethanol-mediated inhibition is largely exerted through the decrease in the NAD-dependent conversion of UDP-glucose (UDPG) to UDP-glucuronic acid, (UDPGA).
Alcohol Research Center, University of Toledo, Toledo, OH 43699, USA.
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D000426:Alcohol Dehydrogenase / Q000037:antagonists & inhibitors / Q000378:metabolism; D000818:Animals; D000831:Animals, Newborn; D002492:Central Nervous System Depressants / Q000008:administration & dosage / Q000494:pharmacology; D002746:Chlorpromazine / Q000008:administration & dosage / Q000378:metabolism; D004791:Enzyme Inhibitors / Q000494:pharmacology; D000431:Ethanol / Q000008:administration & dosage / Q000494:pharmacology*; D005260:Female; D007774:Lactation; D019344:Lactic Acid / Q000494:pharmacology; D008099:Liver / Q000187:drug effects* / Q000378:metabolism; D018811:Maternal Exposure; D009243:NAD / Q000378:metabolism; D011247:Pregnancy; D011619:Psychotropic Drugs / Q000008:administration & dosage / Q000378:metabolism*; D011720:Pyrazoles / Q000494:pharmacology; D051381:Rats; D014532:Uridine Diphosphate Glucose / Q000378:metabolism; D014535:Uridine Diphosphate Glucuronic Acid / Q000378:metabolism
D002492:Central Nervous System Depressants; D004791:Enzyme Inhibitors; D011619:Psychotropic Drugs; D011720:Pyrazoles; D009243:NAD; D014535:Uridine Diphosphate Glucuronic Acid; D019344:Lactic Acid; D000431:Ethanol; C031280:pyrazole; D000426:Alcohol Dehydrogenase; D002746:Chlorpromazine; D014532:Uridine Diphosphate Glucose