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

通过监测非包囊形式药物在皮肤中的浓度来估计经皮给药药物的局部生物利用度。(1)多批次零净通量微透析方法的应用多批次零净通量微透析方法可以缩短采样间隔。阐明了这种方法在体内皮肤中监测非结合形式药物浓度的有效性。(2)脂质微透析（lipoo - md）的应用采用脂质微透析法在体内检测酮洛芬皮肤应用后的光降解产物。缓激肽诱导大鼠肠系膜血管床的三期血管反应中，一系列血管反应相互干扰。动力学分析得到的信息对于讨论药效学分析得到的作用机制是有价值的。抗体联合微透析与常规微透析相比，抗体联合微透析可使替柯普兰的相对回收率提高2 ~ 5倍。植入式控释DDS在皮肤中的体内监测采用微透析法测定两个部位的局部药代动力学特征。在距离DDS 10毫米处测定的轮廓与仅在DDS旁边测定的轮廓完全不同。阐明了精确估计非囊状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.