Netter P, Bannwarth B, Royer-Morrot M J
Département de Rhumatologie, CHU de Nancy-Brabois, Vandoeuvre-Lès-Nancy, France.
Clin Pharmacokinet. 1989 Sep;17(3):145-62. doi: 10.2165/00003088-198917030-00002.
Synovial fluid concentration is considered to be an important determinant of clinical response to non-steroidal anti-inflammatory drugs (NSAIDs). Trans-synovial transport of these drugs is a process of limited diffusion, governed partly by the pharmacological characteristics of NSAIDs and partly by the properties of the joint and joint space themselves. The studies which report simultaneous pharmacokinetics of NSAIDs in both plasma and synovial fluid compartments are of 2 types: (1) some compare the concurrent concentrations of drugs in plasma and joint fluid after a single administration. These provide pharmacokinetic information: (2) others, which conform more closely to the therapeutic conditions, look at synovial fluid and plasma concentrations after repeated administration of the drug. Recent findings on the pharmacokinetics of NSAIDs in synovial fluid are reviewed. These studies reveal 2 types of NSAIDs, according to their pharmacokinetic behaviour. First, there are NSAIDs with a short or intermediate plasma elimination half-life. These drugs equilibrate rapidly relative to their elimination; their peak synovial fluid concentrations occur later and are lower than those in plasma. Several hours after administration there is crossover of the concentration curves, and beyond this point, concentrations in synovial fluid may exceed those in plasma. During prolonged treatment, the synovial fluid concentrations of these NSAIDs fluctuate to a much lesser extent than plasma concentrations. Secondly, there are NSAIDs with a long plasma elimination half-life; their peak concentration in synovial fluid is also lower and later than that in plasma. At steady-state their concentrations (total and free) in synovial fluid are about half those in plasma. Numerous variables must be taken into account in attempts to correlate synovial fluid NSAIDs concentrations with clinical response, including protein binding and determination of both active metabolites and (eventually) the enantiomers.
滑液浓度被认为是对非甾体抗炎药（NSAIDs）临床反应的重要决定因素。这些药物的跨滑膜转运是一个扩散受限的过程，部分受NSAIDs的药理特性影响，部分受关节及关节腔自身特性影响。报告NSAIDs在血浆和滑液隔室同时存在的药代动力学的研究有两种类型：（1）一些研究比较单次给药后血浆和关节液中药物的同时浓度。这些研究提供了药代动力学信息：（2）其他更符合治疗条件的研究则观察药物重复给药后的滑液和血浆浓度。本文综述了NSAIDs在滑液中药代动力学的最新研究结果。根据其药代动力学行为，这些研究揭示了两种类型的NSAIDs。首先，有血浆消除半衰期短或中等的NSAIDs。相对于它们的消除，这些药物平衡迅速；它们在滑液中的峰值浓度出现较晚且低于血浆中的峰值浓度。给药后数小时，浓度曲线会交叉，在此之后，滑液中的浓度可能会超过血浆中的浓度。在长期治疗期间，这些NSAIDs在滑液中的浓度波动程度远小于血浆浓度。其次，有血浆消除半衰期长的NSAIDs；它们在滑液中的峰值浓度也低于血浆中的峰值浓度且出现较晚。在稳态时，它们在滑液中的浓度（总浓度和游离浓度）约为血浆中的一半。在试图将滑液中NSAIDs浓度与临床反应相关联时，必须考虑许多变量，包括蛋白质结合以及活性代谢物和（最终）对映体的测定。
