Estimation of Local Bioavailability for Transdermally Applied Drugs by the Monitoring of Unboud-form Drug Concentrations in the Skin

研究了通过监测药物在皮肤中的药物浓度来评价药物的局部生物利用度。1.药物动力学局部生物利用度的评价(1)多批次零净通量微透析法的应用缩短了采样间隔。(2)用脂微渗析(Lipo-MD)方法在体检测酮洛芬经皮给药后的光降解产物。2.药效学局部生物利用度的评估缓激肽在大鼠肠系膜血管床灌流引起的三相血管反应中，一系列反应相互干扰。从动力学分析中获得的信息对于从药效学分析中获得的作用机制的讨论是有价值的。3.抗体微透析抗体微透析使替考拉宁的相对回收率比传统微透析法提高2-5倍。4.皮肤内植入控释DDS的体内监测通过微透析法在两个位置测定局部药物动力学曲线。在距离DDS 10 mm处测得的轮廓与在DDS旁边测得的轮廓完全不同。阐明了准确估计非结合型药物局部药代动力学的重要性。

Estimation of local bioavailability for transdermally applied drugs by the monitoring of unboud-form drug concentrations in the skin was studied.1.Estimation of pharmacokinetic local bioavailability(1)Application of Muliti-batch Zero-Net Flux microdialysisMuliti-batch Zero-Net Flux microdialysis method enables to shorten the sampling interval. The usefulness of this method in monitoring unboud-formdrug concentrations in the skin in vivo was clarified.(2)Application of Lipo-microdialysis (Lipo-MD)Photodegradation products of ketoprofen after the dermal application were detected by the use of Lipo-MD method in vivo.2.Estimation of pharmacodynamic local bioavailabilityIn the triphasic vascular response induced by bradykinin in rat perfused mesenteric vascular beds, serial responses interfere each other. Information derived from the kinetical analysis is valuable to discuss the mechanism of action obtained by pharmacodynamic analysis.3.Antibody-incorporated microdialysisAntibody-incorporated microdialysis enables to increase the relative recovery for teicoplanin 2 to 5 times compared with that in the conventional microdialysis.4.In vivo monitoring for implanted controlled-release DDS in the skinLocal pharamacokinetic profiles were determined in two positions by microdialysis. The profile determined at 10 mm away from the DDS was completely different from that determined just beside the DDS. The importance of the precise estimation of local pharmacokinetics of unboud-form drugs was clarified.