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Studies on prodrugs utilizing the metabolism in the intestinal microorganisms

Research Project

Project/Area Number 03671028
Research Category

Grant-in-Aid for General Scientific Research (C)

Allocation TypeSingle-year Grants
Research Field Physical pharmacy
Research InstitutionNagasaki University

Principal Investigator

NAKAMURA Junzo  Nagasaki University, School of Pharmaceutical Sciences, Professor, 薬学部, 教授 (30115901)

Project Period (FY) 1991 – 1992
Project Status Completed (Fiscal Year 1992)
Budget Amount *help
¥2,000,000 (Direct Cost: ¥2,000,000)
Fiscal Year 1992: ¥900,000 (Direct Cost: ¥900,000)
Fiscal Year 1991: ¥1,100,000 (Direct Cost: ¥1,100,000)
Keywordsmicroorganism / metabolism / prodrug / rabbit / absorption / salicylic acid / amino acid conjugate / enantiomer / 薬物代謝 / 腸管吸収 / サリチル尿酸 / ドラッグデリバリ-システム
Research Abstract

The significance of the intestinal microorganisms to pharmacokinetics and pharmacology has been emphasized with respect to their ability to metabolize drugs and foreign compounds. We demonstrated that glycine conjugate of salicylic acid was metabolized to salicylic acid by intestinal microorganisms in rabbits, rats and dogs. Furthermore, we examined the effect of fasting or pretreatment with antibiotics on the hydrolysis of salicyluric acid in rabbit intestinal microorganisms. Further study showed that oral treatment with salicylic acid caused severe damage in the rabbit gastric mucosa, but severe damage in the gastric mucosa was not found in rabbits treated with salicyluric acid, suggesting that prodrugs utilizing the metabolism in the intestinal microorganisms may be useful in reducing the gastrointestinal mucosal damage. The elucidation of the effect of amino acid or dipeptide moiety on the fate of salicylic acid is considered to offer a promising approach to develop an effective prodrug of salicylic acid. In the present study, we examined the fate of salicylic acid-L-alanine, -D-alanine, -L-glutamic acid, -L-methionine, -L-tyrosine and -glycylglycine conjugates following oral, intravenous, cecal and rectal administration in rabbits. The accumulation of systematic information on the pharmacokinetic properties of amino acid or dipeptide conjugates of salicylic acid would improve the design of a prodrug which can control the blood concentration and deliver to the large intestine.

Report

(3 results)
  • 1992 Annual Research Report   Final Research Report Summary
  • 1991 Annual Research Report
  • Research Products

    (18 results)

All Other

All Publications (18 results)

  • [Publications] Junzo Nakamura: "Development of a Prodrug of Salicylic Acid,Salicylic Acid-L-alanine Conjugate,Utilizing Hydrolysis by Rabbit Intestinal Microorganisms" 44. 295-299 (1992)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1992 Final Research Report Summary
  • [Publications] Junzo Nakamura: "Unequal Hydrolysis of Salicylic Acid-D-alanine and Salicylic Acid-L-alanine Conjugate in Rabbit Intestinal Microorganisms" Chemical & Pharmaceutical Bulletin. 40. 547-549 (1992)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1992 Final Research Report Summary
  • [Publications] Junzo Nakamura: "A Novel Prodrug of Salicylic Acid,Salicylic Acid-glycylglycine Conjugate,Utitizing the Hydrolysis in Rabbit Intestinal Microorganisms" Chemical & Pharmaceutical Bulletin. 44. 713-716 (1992)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1992 Final Research Report Summary
  • [Publications] Junzo Nakamura: "A Novel Prodrug of Salicylic Acid,Salicylic Acid-glycylglycine Conjugate,Utitizing the Hydrolysis in Rabbit Intestinal Microorganisms" Chemical & Pharmaceutical Bulletin. 40. 2164-2168 (1992)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1992 Final Research Report Summary
  • [Publications] Junzo Nakamura: "Effect of Oral Pretreatment with Antibiotics on the Hydrolysis of Salicylic Acid-tyrosine and Salicylic Acid-methionine Prodrugs in Rabbit Intestinal Microorgabisms" Chemical & Pharmaceutical Bulletin. 40. 2572-2575 (1992)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1992 Final Research Report Summary
  • [Publications] Junzo Nakamura: "Hydrolysis of Salicylic Acid-tyrosine and Salicylic Acid-methionine Prodrugs in the Rabbit" 87. 59-66 (1992)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1992 Final Research Report Summary
  • [Publications] Junzo Nakamura: "Development of a Prodrug of Salicylic Acid, Salicylic Acid-L-ananine Conjugate, Utilizing Hydrolysis by Rabbit Intestinal Microorganisms" Journal of Pharmacy and Pharmacology. 44. 295-299 (1992)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1992 Final Research Report Summary
  • [Publications] Junzo Nakamura: "Unequal Hydrolysis of Salicylic Acid-D-alanine and Salicylic Acid-L-alanine Conjugate in Rabbit Intestinal Microorganisms" Chemical & Pharmaceutical Bulletin. 40. 547-549 (1992)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1992 Final Research Report Summary
  • [Publications] Junzo Nakamura: "A Novel Prodrug of Salicylic Acid, Salicylic Acid-glycylglycine Conjugate, Utilizing the Hydrolysis in Rabbit Intestinal Microorganisms" Journal of Pharmacy and Pharmacology. 44. 713-716 (1992)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1992 Final Research Report Summary
  • [Publications] Junzo Nakamura: "Effect of Oral Pretreatment with Antibiotics on the Hydrolysis of Salicylic Acid-tyrosine and Salicylic Acid-methionine Prodrugs in Rabbit Intestinal Microorganisms" Chemical & Pharmaceutical Bulletin. 40. 2572-2575 (1992)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1992 Final Research Report Summary
  • [Publications] Junzo Nakamura: "Hydrolysis of Salicylic Acid-tyrosine and Salicylic Acid-methionine Prodrugs in the Rabbit" International Journal of Pharmaceutics. 87. 59-66 (1992)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1992 Final Research Report Summary
  • [Publications] Junzo Nakamura: "Development of a prodrug of salicylic acid,salicylic acid-L-alanine conjugate,utilizing hydrolysis by rabbit intestinal microorganisms" Journal of Pharmacy and Pharmacology. 44. 295-299 (1992)

    • Related Report
      1992 Annual Research Report
  • [Publications] Junzo Nakamura: "Unequal hydrolysis of salicylic acid-D-alanine and salicylic acid-L-alanine conjugate in rabbit intestinal microorganisms" Chemical & Pharmaceutical Bulletin. 40. 547-549 (1992)

    • Related Report
      1992 Annual Research Report
  • [Publications] Junzo Nakamura: "A novel prodrug of salicylic acid,salicylic acid-glycylglycine conjugate,utilizing the hydrolysis in rabbit intestinal microorganisms" Journal of Pharmacy and Pharmacology. 44. 713-716 (1992)

    • Related Report
      1992 Annual Research Report
  • [Publications] Junzo Nakamura: "A novel prodrug of salicylic acid,salicylic acid-glutamic acid conjugate utilizing hydrolysis in rabbit intestinal microorganisms" Chemical & Pharmaceutical Bulletin. 40. 2164-2168 (1992)

    • Related Report
      1992 Annual Research Report
  • [Publications] Junzo Nakamura: "Effect of oral pretreatment with antibiotics on the hydrolysis of salicylic acid-tyrosine and salicylic acid-methionine prodrugs in rabbit intestinal microorganisms" Chemical & Pharmaceutical Bulletin. 40. 2572-2575 (1992)

    • Related Report
      1992 Annual Research Report
  • [Publications] Junzo Nakamura: "Hydrolysis of salicylic acid-tyrosine and salicylic acid-methionine prodrugs in the rabbit" International Journal of Pharmaceutics. 87. 59-66 (1992)

    • Related Report
      1992 Annual Research Report
  • [Publications] Junzo Nakamura: "Decrease of Gastrointestinal Mucosal Damage by Salicyluric Acid in Rabbits" Journal of Pharmacy and Pharmacology. 43. 766-773 (1991)

    • Related Report
      1991 Annual Research Report

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Published: 1991-04-01   Modified: 2016-04-21  

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