Estimation of Local Bioavailability for Locally Acting Drug Delivery Systems by Pharmacokinetic- and Pharmacodynamic-Measurement

通过药代动力学和药效学测量估计局部作用药物输送系统的局部生物利用度

• 批准号: 12672216
• 负责人: KUROSAKI Yuji
• 金额: $ 2.18万
• 依托单位: OKAYAMA UNIVERSITY
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (C)
• 财政年份: 2000
• 资助国家: 日本
• 起止时间: 2000 至 2001
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-12672216/
• 关键词: drug delivery system (DDS); local pharmacokinetics; local bioavailability; microdialysis; lipo-microdialysis; percutaneous absorption; colonic absorption; zero-net-flux; 潰瘍性大腸炎; 薬動学; 薬力学

1 Estiniation of local bioavailability for locally acting drug delivery systems by pharmacokinetic- and pharmacodynamic-measurement was studied.1. Application of microdialysis (MD) to measure local pharmacokinetic study(1) Relative recovery, which is the barrier to apply MD in pharmacokinetic study, was strikingly improved by utilizing the lipid emulsions for intravenous injection as the perfusate (Lipo-MD). Both the reliability and the following-up characteristics in Zero-Net-Flux method were improved by the application of Lipo-MD (Lipo-ZNF method) in percutaneous permeation study using butylparaben as the model compound in rats.(2) A MD system was introduced in the in situ closed loop method for studying gastrointestinal absorption study and named Intra-Loop-MD method. This method enabled to get pharmacokinetic parameters in each individual and to reduce the number of experimental animals significantly. The usefulness of this method in estimating populations containing the higher int … More erindividual variation was suggested.2. Kinetic analysis of pharamacological response-time data for estimating local pharmacodynamic availabilityThe usefulness of a kinetic analysis of pharmacological response data was discussed in investigating the ductus arteriosus dilating (ductus-dilating) effect of lipo-PGE_1 (lipid emulsion preparation of prostaglandin E_1 for injection) preparations The ductus-dilating effect of lipo-PGE_1 in an infusion study was simulated by the same PRK model and the estimated parameters in the i.v.-study. The simulation line satisfactorily represented the time-course of the pharmacological response. These findings indicate that PRK modeling based on the intensities of the observed pharmacological response is a meaningful tool in some targeting-type drugs, for which pharmacokinetic analysis itself is meaningless or acquisition of pharmacokinetic data is technically impossible, in expecting the time courses of its pharmacological response in different dosage regimens. Less

研究了通过药代动力学和药效学测量来估计局部作用的药物递送系统的局部生物利用度。微透析（MD）在局部药代动力学研究中的应用(1)静脉注射用脂质乳作为灌注液（lipod -MD）显著提高了相对回收率，这是微透析在药代动力学研究中应用的障碍。将lipoo - md （lipoo - znf法）应用于以对羟基苯甲酸丁酯为模型化合物的大鼠经皮渗透研究，提高了零净通量法的可靠性和随访特性。(2)在原位闭环胃肠吸收研究方法中引入MD系统，命名为Intra-Loop-MD方法。这种方法可以得到每个个体的药代动力学参数，并且可以显著减少实验动物的数量。这种方法在估计含有较高的个体差异的种群时是有用的。药理学反应时间数据的动力学分析用于估计局部药效学有效性探讨药理学反应数据动力学分析在研究脂质乳剂pge_1（注射用前列腺素E_1脂质乳剂）制剂的动脉导管扩张（导管扩张）作用中的作用。脂质pge_1在输注研究中的扩张作用采用相同的PRK模型和静脉注射研究中的估计参数进行模拟。模拟线令人满意地代表了药理学反应的时间过程。这些发现表明，基于观察到的药理反应强度的PRK建模对于某些靶向型药物来说是一种有意义的工具，对于这些药物来说，药代动力学分析本身没有意义，或者在技术上不可能获得药代动力学数据，以预测其在不同剂量方案下的药理反应的时间过程。少

项目成果

政岡祥江, 岡崎宏美, 黒崎勇二, 川崎博己, 谷田宣文, 後藤 武: "ブテソニドの大腸吸収動態の部位差:P-糖蛋白様排出系の関与"Drug Delivery System. 16. 339 (2001)

Yoshie Masaoka、Hiromi Okazaki、Yuji Kurosaki、Hiromi Kawasaki、Nobufumi Tanida、Takeshi Goto：“布替奈德结肠吸收动力学的区域差异：P-糖蛋白样排泄系统的参与”药物输送系统。

Yoshie Masaoka, Hiromi Okazaki, Yuji Kurosaki, Hiromu Kawasaki: "Colonic absorption of steroids in ulcerative colitis rats."Xenobio. Metabol. Dispos.. 16 (Suppl.). S203 (2001)

Yoshie Masaoka、Hiromi Okazaki、Yuji Kurosaki、Hiromu Kawasaki：“溃疡性结肠炎大鼠中类固醇的结肠吸收。”Xenobio。

政岡祥江, 岡崎宏美, 黒崎勇二, 川崎博己: "病態時の経口ステロイド剤の大腸吸収特性:潰瘍性大腸炎モデルラットでの検討"薬物動態(Xenobio.Metabol.Dispos.). 16(Suppl.). S203 (2001)

Yoshie Masaoka、Hiromi Okazaki、Yuji Kurosaki、Hiroki Kawasaki：“病理条件下口服类固醇的结肠吸收特征：溃疡性结肠炎模型大鼠的调查”药代动力学（Xenobio.Metabol.Dispos.）16（增刊）.S203（2001）。

Yamato Sano, Rieko Kawashima, Yuji Kurosaki, Hiromu Kawasaki: "Dermal pharmacokinetic studies by Lipo-Zero-Net-Flux method."J. Pharm. Sci. Technol. Japan. 62 (Suppl.). 96 (2002)

Yamato Sano、Rieko Kawashima、Yuji Kurosaki、Hiromu Kawasaki：“通过 Lipo-Zero-Net-Flux 方法进行皮肤药代动力学研究。”J.

佐野大和, 川島理恵子, 黒崎勇二, 川崎博己: "Lipo-Microdialysis法による薬物の皮膚局所動態の評価:Zero-Net-Flux法への応用"薬物動態(Xenobio.Metabol.Dispos.). 16(Suppl.). S210 (2001)

Yamato Sano、Rieko Kawashima、Yuji Kurosaki、Hiroki Kawasaki：“通过脂质微透析方法评估药物的皮肤局部动力学：零净通量方法的应用”药代动力学（Xenobio.Metabol.Dispos.）。 .S210 (2001)