Publication: Biphasic Effect of Methadone on Hepatic Drug Metabolism
2
Issued Date
1987-01-01
Resource Type
ISSN
15353699
00379727
00379727
Other identifier(s)
2-s2.0-0023113457
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Mahidol University
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SCOPUS
Bibliographic Citation
Proceedings of the Society for Experimental Biology and Medicine. Vol.184, No.1 (1987), 40-46
Suggested Citation
S. Komthong, K. Yoovathaworn, A. Thithapandha Biphasic Effect of Methadone on Hepatic Drug Metabolism. Proceedings of the Society for Experimental Biology and Medicine. Vol.184, No.1 (1987), 40-46. doi:10.3181/00379727-184-42443 Retrieved from: https://repository.li.mahidol.ac.th/handle/123456789/15318
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Title
Biphasic Effect of Methadone on Hepatic Drug Metabolism
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Abstract
When methadone HC1 (30 mg/kg, po) was given acutely to mice, it was found to inhibit drug metabolism as evidenced by a prolongation of hexobarbital sleeping time and zoxazolamine paralysis time. Pharmacokinetic studies revealed that this acute dose of the narcotic analgesic could also prolong the plasma half-life of aminopyrine without any change in its volume of distribution. When added to the incubation mixture containing 10,000 g mouse liver supernatant fraction and a complete system for measuring aminopyrine.N-demethylase or aniline hydroxylase, metadone showed a dose-dependent inhibition of the enzymes; the former enzyme was inhibited to a greater extent than the latter one. However, subacute treatment of mice with methadone HC1 (30 mg/kg, po, twice daily for 3 days) resulted in increases in liver weight, microsomal protein, and cytochrome P-450 content in consonant with the increased activities of four hepatic drug-metabolizing enzymes: aminopyrine N-demethylase, aniline hydroxylase, p-nitroanisole, O-demethylase, and benzphetamine N-demethylase. Moreover, both hexobarbital sleeping time and zoxazolamine paralysis time were shortened. The plasma half-life of aminopyrine was decreased. These changes were prevented by simultaneous administration of puromycin diHCl (80 mg/kg, ip). Methadone thus seems to act in a manner very similar to that of propoxyphene or SKF-525A, acting as a potent inhibitor of hepatic drug metabolism when given acutely and as an inducer when given subacutely. © 1987, SAGE Publications. All rights reserved.