Busch U, Engelhardt G
Department of Pharmacokinetics, Dr Karl Thomae GmbH, Biberach/Riss, FRG.
Drugs Exp Clin Res. 1990;16(2):49-52.
Using the new non-steroidal anti-inflammatory agent meloxicam (Mel), comparative investigations on pharmacokinetics and metabolism show good agreement between results in man and in the rat. To demonstrate preferential localization of the compound in inflamed sites, the distribution of the radiolabelled compound in arthritic joints of rats was studied using autoradiography. For that purpose an arthritis-inducing antigen was given to male albino rats. Twenty one days after antigen injection, all animals were given [14C]Mel orally. At three different times after receiving the labelled compound, the animals were sacrificed under anaesthesia. Tissue sections from each leg of each animal were taken for autoradiography. Sections were stained after film exposure using Masson-Goldner staining. The radiolabelled compound was preferentially localized in the areas which stained for inflamed connective tissue. The distribution pattern described persists beyond 24 h post-application. The figures indicate a highly efficient distribution of the radioactivity into chronically inflamed tissue of the hind foot-pads. Since negligible radioactivity was found in the front foot-pads, it is concluded that uptake into inflamed tissue is favoured.
使用新型非甾体抗炎药美洛昔康（Mel）进行的药代动力学和代谢对比研究表明，人体和大鼠的研究结果具有良好的一致性。为了证明该化合物在炎症部位的优先定位，采用放射自显影技术研究了放射性标记化合物在大鼠关节炎关节中的分布。为此，给雄性白化大鼠注射致关节炎抗原。抗原注射21天后，所有动物口服[14C]Mel。在接受标记化合物后的三个不同时间，将动物麻醉处死。取每只动物每条腿的组织切片进行放射自显影。胶片曝光后，切片用马森-戈德纳染色法染色。放射性标记化合物优先定位于炎症结缔组织染色的区域。所述分布模式在给药后24小时以上持续存在。这些数据表明放射性物质高效分布到后脚垫的慢性炎症组织中。由于在前脚垫中发现的放射性物质可忽略不计，因此得出结论，该化合物易于摄取到炎症组织中。
