Department of Pharmaceutical Sciences, Leslie Dan Faculty of Pharmacy, University of Toronto, 144 College Street, Toronto, ON, M5S 3M2, Canada.
Expert Rev Clin Pharmacol. 2012 Jan;5(1):69-89. doi: 10.1586/ecp.11.66.
Inflammation plays a critical role in host defense, maintaining cellular and tissue integrity following chemical, physical and biological insults. Inflammation presents in a variety of acute and chronic disease states and can contribute to disease resolution or progression depending upon the type, magnitude and duration of response. Importantly, it has been shown to modulate pharmacokinetic processes leading to variability in therapeutic drug response. Membrane-associated drug transporters are important determinants of drug disposition and pharmacokinetics and we, among others, have identified inflammation-mediated changes in their expression and regulation. Here, we discuss the current state of knowledge on drug transporter expression during acute and chronic inflammatory conditions and postulate how the altered expression of these transporters may modify the pharmacokinetics and pharmacodynamics of clinically important therapeutics. As understanding determinants of interpatient variability in therapeutic drug response is essential to the practice of medicine, this area of research warrants future clinical focus.
炎症在宿主防御中起着关键作用，可在化学、物理和生物损伤后维持细胞和组织完整性。炎症存在于多种急性和慢性疾病状态中，并可能取决于反应的类型、程度和持续时间而有助于疾病的缓解或进展。重要的是，它已被证明可调节药代动力学过程，导致治疗药物反应的变异性。膜相关药物转运体是药物处置和药代动力学的重要决定因素，我们和其他人已经确定了它们的表达和调节在炎症介导下发生的变化。在这里，我们讨论了在急性和慢性炎症情况下药物转运体表达的最新知识，并推测这些转运体的表达改变可能如何改变临床重要治疗药物的药代动力学和药效学。由于了解治疗药物反应的个体间变异性的决定因素对于医学实践至关重要，因此这一研究领域值得未来的临床关注。
