Havemann D
Fortschr Med. 1977 Jan 20;95(3):177-81.
The kinetic behaviour of radioactively labeled acetylsalicylic acid (ASA), phenylbutazone (PBZ), indometacin and dexamethasone in rabbits with knee joints experimentally inflamed can be summarized as follows: 1. Under control (non-inflammation) conditions as well as during inflammation, subthreshold doses of 14C-ASA intravenously (i.v.) administered were eliminated from the blood in a fast and slow biphasis process. The changes of the concentration in the perfusion fluid were very similar compared to the changes in the blood. However, they were enhanced during experimentally induced synovitis. 2. Subthreshold does of 3H-phenylbutazone i.v. administered were eliminated from the blood like 14C-ASA in a biphasic process. During an experimentally produced inflammation of the joints, the blood level decreased rapidly. The concentration of radioactivity in the perfusion fluid was very low. 3. In constrast, 3H-indometacin injected like ASA and PBZ in subtherapeutic dosage diappeared from the blood in a threephasic process. The uptake into both the normal and the inflamed synovial space was biphasic. Under both conditions the perfusion fluid contained low concentrations of the drug. 4. 3H-dexamethasone (subtherapeutic dosage) displayed a biphasis fall of concentration in the blood: a fast first phase and a slower second phase. With inflammation of the kneejoint, the elimination was characterized by a three-phase slope and was significantly faster compared with control animals. While the alterations of ASA and indometacin level in the perfusion fluid were corresponding to the decrease of the blood concentration, the uptake of dexamethasone into the synovial space did not show any change. 5. Under control conditions. 3H-dexamethasone (subthreshold doses) injected intraariculary was rapidly detectalbe in the blood. However, systemic absorption was considerably faster under inflammation conditions; the blood level was lower than following administration of 3H-dexamethasone into the normal knee-joint, the distribution from which was not uniform. After pretreating the animals with high does of hydrocortisonacetate, the i.v. application of 3H-dexamethasone was followed by a delayed first phase of the biphasis process of elimination. 6. Autoradiographic studies revealed 14C-ASA to be accumulated in the synovial fluid under normal conditions and in the periaricular connective tissue under inflammation conditions.
放射性标记的乙酰水杨酸（ASA）、保泰松（PBZ）、吲哚美辛和地塞米松在实验性膝关节发炎兔子体内的动力学行为可总结如下：1. 在对照（非炎症）条件下以及炎症期间，静脉注射（i.v.）亚阈值剂量的14C - ASA会以快速和缓慢的双相过程从血液中消除。与血液中的变化相比，灌注液中浓度的变化非常相似。然而，在实验性诱导的滑膜炎期间，这些变化会增强。2. 静脉注射亚阈值剂量的3H - 保泰松会像14C - ASA一样以双相过程从血液中消除。在实验性关节炎症期间，血液水平迅速下降。灌注液中的放射性浓度非常低。3. 相比之下，以亚治疗剂量像ASA和PBZ一样注射的3H - 吲哚美辛从血液中消失的过程为三相。进入正常和发炎滑膜腔的摄取是双相的。在这两种情况下，灌注液中药物浓度都很低。4. 3H - 地塞米松（亚治疗剂量）在血液中浓度呈双相下降：快速的第一相和较慢的第二相。膝关节发炎时，消除过程的特征是三相斜率，且与对照动物相比明显更快。虽然灌注液中ASA和吲哚美辛水平的变化与血液浓度的降低相对应，但地塞米松进入滑膜腔的摄取没有显示任何变化。5. 在对照条件下，关节内注射的3H - 地塞米松（亚阈值剂量）在血液中很快就能检测到。然而，在炎症条件下全身吸收要快得多；血液水平低于将3H - 地塞米松注入正常膝关节后的水平，其分布不均匀。在用高剂量醋酸氢化可的松预处理动物后，静脉注射3H - 地塞米松后消除双相过程的第一相会延迟。6. 放射自显影研究表明，14C - ASA在正常情况下积聚在滑液中，在炎症情况下积聚在关节周围结缔组织中。
