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Dexamethasone 21-Sulfate Improves the Therapeutic Properties of Dexamethasone Against Experimental Rat Colitis by Specifically Delivering the Steroid to the Large Intestine

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Abstract

Purpose

We investigated in vivo-colon targetability and therapeutic properties of DS against experimental rat colitis.

Methods

The systemic absorption and colonic delivery of D after oral administration of DS was analyzed by examining the concentration of drugs in the GI tract, plasma, urine and feces. Therapeutic activity of DS was determined using a TNBS-induced rat colitis model. Adrenal suppression by DS administration was evaluated by monitoring the concentration of ACTH and corticosterone in the plasma.

Results

DS administered orally was delivered efficiently to the large intestine resulting in D accumulation at the target site. In addition, DS was not detectable in the plasma and was detected very low in the urine after DS administration. The fecal and urinary recovery of D (after DS administration) was much greater and less than that after D administration, suggesting that DS should exhibit enhanced therapeutic activity and reduced systemic side effects. Consistent with this notion, DS was more effective than D in healing rat colitis. Moreover, oral administration of either D or DS reduced the plasma corticosterone and ACTH levels from the normal levels, which is significantly greater for D.

Conclusion

DS is a promising colon specific prodrug that improves therapeutic properties of D

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Abbreviations

ACTH:

Adrenocorticotropic hormone

CD:

Crohn’s disease

D:

Dexamathasone

DS:

Dexamathasone 21-sulfate or sulfate conjugated dexamathasone

DSI:

Distal small intestine

IBD:

Inflammatory bowel disease

PSI:

Proximal small intestine

TNBS:

2,4,6-Trinitrobenzenesulfonic acid

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Authors and Affiliations

  1. Laboratory of Biomedicinal/Medicinal Chemistry, College of Pharmacy, Pusan National University, Pusan, 609-735, Republic of Korea

    Inho Kim, Younghyun Lee, Sungchae Hong, Jungoh Han, Sunhwa Jung, Yunjin Jung & Young Mi Kim

  2. Urologic Oncology Branch, Center for Cancer Research, National Cancer Institute, Bethesda, Maryland, 20892, USA

    Hyesik Kong

Authors
  1. Inho Kim
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  2. Hyesik Kong
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  3. Younghyun Lee
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  4. Sungchae Hong
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  5. Jungoh Han
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  6. Sunhwa Jung
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  7. Yunjin Jung
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  8. Young Mi Kim
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Correspondence to Yunjin Jung or Young Mi Kim.

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Kim, I., Kong, H., Lee, Y. et al. Dexamethasone 21-Sulfate Improves the Therapeutic Properties of Dexamethasone Against Experimental Rat Colitis by Specifically Delivering the Steroid to the Large Intestine. Pharm Res 26, 415–421 (2009). https://doi.org/10.1007/s11095-008-9758-1

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  • DOI: https://doi.org/10.1007/s11095-008-9758-1

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