Pharmaceutical Research

, Volume 22, Issue 8, pp 1406–1410 | Cite as

Inhibitory Effects of Various Beverages on Ritodrine Sulfation by Recombinant Human Sulfotransferase Isoforms SULT1A1 and SULT1A3

  • Haruka Nishimuta
  • Masayuki Tsujimoto
  • Kenichiro Ogura
  • Akira Hiratsuka
  • Hisakazu Ohtani
  • Yasufumi Sawada
Short Communication

Purpose

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 ≥95%.

Conclusion

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 β2-agonists, and lead to an increase in the clinical effects or adverse reactions.

Key Words

drug-food interaction enzyme inhibitors intestinal bioavailability ritodrine sulfotransferase 

Abbreviations

PAPS

3′-phosphoadenosine 5′-phosphosulfate

SULT

sulfotransferase

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Copyright information

© Springer Science + Business Media, Inc. 2005

Authors and Affiliations

  • Haruka Nishimuta
    • 1
  • Masayuki Tsujimoto
    • 1
  • Kenichiro Ogura
    • 2
  • Akira Hiratsuka
    • 2
  • Hisakazu Ohtani
    • 1
  • Yasufumi Sawada
    • 1
  1. 1.Department of Medico-Pharmaceutical Sciences, Graduate School of Pharmaceutical SciencesKyushu UniversityFukuokaJapan
  2. 2.Department of Drug Metabolism and Molecular Toxicology, School of PharmacyTokyo University of Pharmacy and Life ScienceTokyoJapan

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