Inhibitory effects of various beverages on ritodrine sulfation by recombinant human sulfotransferase isoforms SULT1A1 and SULT1A3.
OBJECTIVE
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.


METHODS
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.


RESULTS
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%.


CONCLUSIONS
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.
Nishimuta
Haruka
H
Department of Medico-Pharmaceutical Sciences, Graduate School of Pharmaceutical Sciences, Kyushu University, Higashi-ku, Fukuoka-shi, Fukuoka, 812-8582, Japan.
Tsujimoto
Masayuki
M
Ogura
Kenichiro
K
Hiratsuka
Akira
A
Ohtani
Hisakazu
H
Sawada
Yasufumi
Y
D000318:Adrenergic beta-Agonists / Q000737:chemistry*; D000465:Algorithms; D015239:Arylsulfotransferase / Q000737:chemistry*; D001345:Autoradiography; D001628:Beverages; D001682:Biological Availability; D002957:Citrus; D018565:Food-Drug Interactions; D006801:Humans; D007527:Isoenzymes / Q000737:chemistry; D007700:Kinetics; D011994:Recombinant Proteins / Q000737:chemistry; D012312:Ritodrine / Q000737:chemistry*; D015238:Sulfotransferases / Q000737:chemistry*; D013662:Tea
D000318:Adrenergic beta-Agonists; D007527:Isoenzymes; D011994:Recombinant Proteins; D013662:Tea; D015238:Sulfotransferases; D015239:Arylsulfotransferase; C117544:SULT1A1 protein, human; C403170:monoamine-sulfating phenol sulfotransferase; D012312:Ritodrine