In vivo and in vitro effect of chelating agents on drug metabolizing enzymes of the rat.
Rats given calcium disodium ethylenediaminetetraacetic acid (CaNa2EDTA), diethylenetriaminepentaacetic acid (DTPA), dimercaprol, p-aminosalicylic acid (PAS), or d-penicillamine (penicillamine) i.p. for 7 successive days showed a significant decrease in the activity of hepatic microsomal benzphetamine N-demethylase. There was no appreciable change in the microsomal cytochrome P-450 concentration. In vitro incubation of the chelating drugs with liver microsomes isolated from rats pre-treated with phenobarbital caused no significant loss of the hemoprotein. The decreased rate of benzphetamine metabolism in microsomal preparations from rats, pretreated with the chelating drugs, may be attributed partly to hepatic depletion of essential trace elements by the chelating drugs.
D010131:Aminosalicylic Acid / Q000378:metabolism*; D000636:Aminosalicylic Acids / Q000378:metabolism*; D000818:Animals; D001589:Benzphetamine / Q000378:metabolism*; D003577:Cytochrome P-450 Enzyme System / Q000378:metabolism; D004112:Dimercaprol / Q000378:metabolism*; D008297:Male; D008862:Microsomes, Liver / Q000187:drug effects* / Q000201:enzymology; D010396:Penicillamine / Q000378:metabolism*; D004369:Pentetic Acid / Q000378:metabolism*; D010627:Phenethylamines / Q000378:metabolism*; D051381:Rats
D000636:Aminosalicylic Acids; D010627:Phenethylamines; D004112:Dimercaprol; D001589:Benzphetamine; D010131:Aminosalicylic Acid; D004369:Pentetic Acid; D003577:Cytochrome P-450 Enzyme System; D010396:Penicillamine