Enhanced metabolism of methyprylon (cas 125-64-4), meprobamate, and chlordiazepoxide hydrochloride after chronic feeding of a low dietary level of DDT to male and female rats
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Add time:09/27/2019 Source:sciencedirect.com
A daily intake of 0.04–0.10 mg of dichlorodiphenyltrichloroethane (DDT; 1,1,1-trichloro-2,2-bis (p-chlorophenyl)ethane), levels which are within the daily dietary intake of humans, by male and female rats significantly (P < 0.05) enhanced the hepatic drug metabolizing enzyme activity and shortened the duration of drug action of 3 nonbarbiturate depressants during the intervals of 4, 8, 12, 16, and 20 weeks of chronic DDT feeding. The nonbarbiturate depressants studied were: methyprylon (Noludar; 3,3-diethyl-5-methyl-2,4-piperidinedione), meprobamate (Miltown; 2-methyl-2-n-propyl-1,3-propanediol dicarbamate), and chlordiazepoxide hydrochloride (Librium; 7-chloro-2-methylamino-5-phenyl-3H-1,4-benzodiazepine 4-oxide hydrochloride). The hepatic enzyme systems from male rats appeared to metabolize these drugs at a faster rate than those from female rats. A significantly (P < 0.05) enhanced metabolism was maintained for these 3 drugs by each sex even after withdrawal of DDT from the diet for 12 weeks. A sex difference in the retention of DDT in the adipose tissue was noted. The concentration of DDT plus its metabolite(s) was higher in the fat from female rats than in corresponding male fat; this was true for both control and experimental animals. The concentration of DDT plus its metabolite(s) in the fat of each sex declined after withdrawal from the DDT diet and, after 12 weeks, the concentration of DDT plus its metabolite(s) in rat fat (11–21 μg/g fat) had approached the reported DDT content in the adipose tissue of the human population.
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