IN VITRO AND IN VIVO INTERACTIONS OF Δ^8-TETRAHYDROCANNABINOL AND ITS METABOLITES WITH HEPATIC MICROSOMAL DRUG METABOLIZING ENZYME SYSTEMS OF MICE
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概要
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Interactions of Δ^8-tetrahydrocannabinol (Δ^8-THC) and its metabolites, 11-hydroxy-Δ^8-THC, 11-oxo-Δ^8-THC and Δ^8-THC-11-oic acid, with hepatic microsomal drug metabolizing enzyme systems were studied in vitro and in vivo using mice. All the cannabinoids used were shown to produce a type I spectral change of cytochrome P-450 in hepatic microsomes. The apparent binding affinities (K_s) for Δ^8-THC, 11-hydroxy-Δ^8-THC, 11-oxo-Δ^8-THC and Δ^8-THC-11-oic acid were 5.2,169.6,33.2 and 148.8μM, respectively. Δ^8-THC, 11-oxo-Δ^8-THC and Δ^8-THC-11-oic acid (100μM) caused a significant stimulation of NADPH oxidation in vitro with microsomes. In addition, Δ^8-THC (20,40 and 80μM) markedly inhibited p-nitroanisole O-demethylase and aniline hydroxylase in microsomes. 11-Hydroxy-Δ^8-THC and 11-oxo-Δ^8-THC also showed the inhibitory effect, but to lesser extents. Furthermore, single pretreatments with Δ^8-THC and 11-oxo-Δ^8-THC (30 mg/kg, i.v.) significantly decreased activities of p-nitroanisole O-demethylase and aniline hydroxylase in hepatic microsomes, accompanying a decrease of cytochrome P-450 content in case of Δ^8-THC. On the other hand, all these pretreatments except for that with Δ^8-THC-11-oic acid showed a stimulatory effect on p-nitrophenol glucuronidation with hepatic microsomes, in contrast to an inhibitory effect in vitro.
- 公益社団法人日本薬学会の論文
著者
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Yamamoto Ikuo
北陸大学 薬 衛化
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WATANABE KAZUHITO
School of Pharmacy, Hokuriku University
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Yoshimura Hidetoshi
Faculty Of Pharmaceutical Sciences Kyushu University
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Oguri Kazuta
Faculty Of Pharmaceutical Sciences Kyushu University
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Oguri Kazuta
School Of Pharmacy Hokuriku University
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Watanabe Kazuhito
Faculty Of Pharmaceutical Sciences Kyushu University
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Yamamoto Ikuo
School Of Pharmaceutical Sciences Kyushu University Of Health And Welfare
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