Development of a new method for bioavailability assessment using a pharmacokineic/pharmacodynamic model

使用药代动力学/药效学模型开发生物利用度评估新方法

基本信息

  • 批准号:
    05671797
  • 负责人:
  • 金额:
    $ 1.34万
  • 依托单位:
  • 依托单位国家:
    日本
  • 项目类别:
    Grant-in-Aid for General Scientific Research (C)
  • 财政年份:
    1993
  • 资助国家:
    日本
  • 起止时间:
    1993 至 1994
  • 项目状态:
    已结题

项目摘要

The rapid development of automated synthetic and recombinant DNA methods of peptide preparation have made available a great variety of peptide and peptide analogs of potential therapeutic value. Example include synthetic peptide hormons (such as insulin, vasopressin, calcitonin, somatostatin, etc.), peptide analogs, renin inhibitors, and angiotensin converting enzyme inhibitors are currently available for clinical use. The usual route of adsministration of these compounds were intravascular, intramuscular or subcutaneous ; however, a number of side effects due to injection have been reported. Although, oral, rectal or nasal route have attracted ateension, because of its potential to improve the side-effects, the assesment of bioavailability after extravascular administration of these drugs are extremely difficult. The objective of this project is to develop a new method for bioavailability assessment and to optimise the dosage regimens after oral nasal administration of these drugs. Captopril (CP), salmon calcitonin (sCT) and arginine vasopressin (AVP) were used as model compounds. A pharmacokinetic (PK) / pharmacodynamic (PD) model, including physiological regulation systems, such as arterial pressure control system, plasma calcium regulation system and/or urinary sodium regulation system was constructued, and the pharmacological data after extravascular administraiton of these drugs were analyzed. Results indicated that the rate and extent of bioavailability of these drugs were precisely estimated by the PK/PD model.
肽制备的自动化合成和重组DNA方法的快速发展使得可获得具有潜在治疗价值的多种肽和肽类似物。实例包括合成肽类药物(如胰岛素、血管加压素、降钙素、生长抑素等),肽类似物、肾素抑制剂和血管紧张素转化酶抑制剂目前可用于临床应用。这些化合物的常用给药途径为血管内、肌内或皮下给药;然而,已报告了由于注射引起的许多副作用。虽然口服、直肠或鼻腔给药已引起广泛关注,但由于其潜在的改善副作用的潜力,血管外给药后的生物利用度评估是非常困难的。本项目的目的是开发一种新的生物利用度评估方法,并优化这些药物经口鼻腔给药后的给药方案。以卡托普利(CP)、鲑鱼降钙素(sCT)和精氨酸加压素(AVP)为模型化合物。建立了包括动脉血压调节系统、血浆钙调节系统和/或尿钠调节系统等生理调节系统在内的药代动力学(PK)/药效学(PD)模型,分析了这些药物血管外给药后的药理学数据。结果表明,PK/PD模型能准确估计这些药物的生物利用度。

项目成果

期刊论文数量(3)
专著数量(0)
科研奖励数量(0)
会议论文数量(0)
专利数量(0)
Kazuhiro Morimoto: "Effects of proteolytic enzyme inhibitor on nasal absorption of salmon caicitonin in rats" International Journal of Pharmaceutics. 113. 1-8 (1995)
Kazuhiro Morimoto:“蛋白水解酶抑制剂对大鼠鲑鱼降钙素鼻吸收的影响”国际药剂学杂志。
  • DOI:
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    0
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  • 通讯作者:
森本一洋: "Effects of proteolytic enzyme inhibitors on nasal absorption of salmon calcitonin in rats" International Journal of Pharmaceutics. 113. 1-8 (1995)
Kazuhiro Morimoto:“蛋白水解酶抑制剂对大鼠鲑鱼降钙素鼻吸收的影响”国际药剂学杂志 113. 1-8 (1995)。
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    0
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KAKEMI Masawo其他文献

KAKEMI Masawo的其他文献

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{{ truncateString('KAKEMI Masawo', 18)}}的其他基金

Optimization of Dosage Regimens Using a Mechanism-based PK-PD Model
使用基于机制的 PK-PD 模型优化剂量方案
  • 批准号:
    18590159
  • 财政年份:
    2006
  • 资助金额:
    $ 1.34万
  • 项目类别:
    Grant-in-Aid for Scientific Research (C)
Optimization of dosage regimen using a mechanism-based pharmacokinetic-pharmacodynamic modeling
使用基于机制的药代动力学-药效学模型优化剂量方案
  • 批准号:
    15590144
  • 财政年份:
    2003
  • 资助金额:
    $ 1.34万
  • 项目类别:
    Grant-in-Aid for Scientific Research (C)
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