给药方案在控制间接药效学反应中的作用。

Role of dosage regimen in controlling indirect pharmacodynamic responses.

作者信息

Gobburu J V, Jusko W J

机构信息

Department of Pharmaceutics, State University of New York, Buffalo, NY 14260, USA.

出版信息

Adv Drug Deliv Rev. 2001 Mar 1;46(1-3):45-57. doi: 10.1016/s0169-409x(00)00132-0.

DOI:10.1016/s0169-409x(00)00132-0

PMID:11259832

Abstract

The role of drug delivery in controlling indirect pharmacodynamic responses was assessed via computer simulations and literature review. Simulations of responses related to basic indirect response mechanisms were performed for various drug input rates which allowed the importance of drug delivery rate on the overall pharmacodynamic response to be evaluated. Response versus time profiles of integrated or net responses and efficiency were examined. Rate of drug input has the greatest influence on the area under the effect curve when doses are larger and target drug concentrations are above the IC(50)/SC(50). The pharmacodynamics of drugs which elicit indirect pharmacologic responses such as corticosteroids, diuretics, growth hormone, erythropoietin and insulin indicate that sustained drug delivery enhances the therapeutic efficiency and pharmacodynamic availability.

摘要

通过计算机模拟和文献综述评估了药物递送在控制间接药效学反应中的作用。针对各种药物输入速率，对与基本间接反应机制相关的反应进行了模拟，从而能够评估药物递送速率对整体药效学反应的重要性。研究了综合或净反应以及效率的反应-时间曲线。当剂量较大且目标药物浓度高于IC(50)/SC(50)时，药物输入速率对效应曲线下面积的影响最大。引发间接药理反应的药物，如皮质类固醇、利尿剂、生长激素、促红细胞生成素和胰岛素，其药效学表明持续药物递送可提高治疗效率和药效学可用性。