Nishimuta Haruka, Tsujimoto Masayuki, Ogura Kenichiro, Hiratsuka Akira, Ohtani Hisakazu, Sawada Yasufumi
Department of Medico-Pharmaceutical Sciences, Graduate School of Pharmaceutical Sciences, Kyushu University, Higashi-ku, Fukuoka-shi, Fukuoka, 812-8582, Japan.
Pharm Res. 2005 Aug;22(8):1406-10. doi: 10.1007/s11095-005-5263-y. Epub 2005 Aug 3.
Ritodrine is known to undergo extensive presystemic sulfation in the intestinal mucosa, and its bioavailability is as low as 30%. Accordingly, inhibition of intestinal sulfation may lead to an increase in the bioavailability of ritodrine. In this study, we aimed to investigate the activities of ritodrine sulfation by SULT1A1, which is expressed predominantly in the liver, and SULT1A3, which is expressed predominantly in the intestine, as well as the inhibitory effects of beverages on their activities.
We investigated ritodrine sulfation by using recombinant human sulfotransferase (SULT) 1A1 and SULT1A3 in an in vitro study. Next, we investigated the inhibitory effects of grapefruit juice, orange juice, green tea, and black tea on ritodrine sulfation.
Sulfation of ritodrine by SULT1A3 was much higher than that by SULT1A1, suggesting that the bioavailability of ritodrine may be limited by intestinal SULT1A3. The ritodrine sulfation activities of SULT1A1 and SULT1A3 were significantly inhibited by all beverages examined at a concentration of 10%. Green tea and black tea exhibited potent inhibition; even at a concentration of 5%, they both inhibited SULT1A1 by 100% and SULT1A3 by >or=95%.
Our results suggest that concomitant ingestion of beverages such as green tea and black tea may increase the bioavailability of orally administered ritodrine, and perhaps other beta2-agonists, and lead to an increase in the clinical effects or adverse reactions.
已知利托君在肠道黏膜中会经历广泛的首过硫酸化，其生物利用度低至30%。因此，抑制肠道硫酸化可能会导致利托君生物利用度增加。在本研究中，我们旨在研究主要在肝脏中表达的SULT1A1和主要在肠道中表达的SULT1A3对利托君硫酸化的活性，以及饮料对其活性的抑制作用。
我们在体外研究中使用重组人磺基转移酶（SULT）1A1和SULT1A3研究利托君的硫酸化。接下来，我们研究了葡萄柚汁、橙汁、绿茶和红茶对利托君硫酸化的抑制作用。
SULT1A3对利托君的硫酸化作用远高于SULT1A1，这表明利托君的生物利用度可能受肠道SULT1A3的限制。所有检测的饮料在浓度为10%时均显著抑制SULT1A1和SULT1A3的利托君硫酸化活性。绿茶和红茶表现出强效抑制作用；即使在浓度为5%时，它们对SULT1A1的抑制率均为100%，对SULT1A3的抑制率≥95%。
我们的结果表明，同时摄入绿茶和红茶等饮料可能会增加口服利托君以及其他β2激动剂的生物利用度，并导致临床效果或不良反应增加。
