Houghton G W, Dennis M J, Rigler E D, Parsons R L
Eur J Drug Metab Pharmacokinet. 1984 Jul-Sep;9(3):201-4. doi: 10.1007/BF03189642.
The urinary pharmacokinetics of ketoprofen were compared after administration of single doses of standard ketoprofen capsules or two sustained-release pellet formulations of ketoprofen to nine healthy volunteers, using a specific and sensitive high-performance liquid chromatographic assay procedure. The sustained-release pellet formulation with the faster in vitro release characteristics was shown to be bioequivalent to ketoprofen capsules ('Orudis'). The mean (+/- standard deviation) apparent elimination half-life of ketoprofen after this sustained-release formulation was 7.4 +/- 3.1 h, compared with 4.1 +/- 0.85 h after ketoprofen capsules. The sustained-release formulation with the slower in vitro dissolution characteristics also exhibited slower in vivo dissolution, but was only 65% bioavailable, compared to ketoprofen capsules. A disproportionately large degree of elimination of free ketoprofen was observed between 0-6 h after dosing with ketoprofen capsules. This result could be explained by a saturable mechanism in the metabolism of ketoprofen to its glucuronide. however, since the renal excretion of free ketoprofen is not a major route of ketoprofen elimination, relatively large alterations in this parameter will not markedly alter elimination half-life or area under the plasma ketoprofen concentration against time curve. Thus, the clinical significance of such a mechanism is probably negligable.
采用一种特异且灵敏的高效液相色谱分析方法，在9名健康志愿者中比较了单次服用标准酮洛芬胶囊或两种酮洛芬缓释微丸制剂后酮洛芬的尿药代动力学。体外释放特性较快的缓释微丸制剂显示与酮洛芬胶囊（“奥鲁地”）生物等效。服用这种缓释制剂后，酮洛芬的平均（±标准差）表观消除半衰期为7.4±3.1小时，而服用酮洛芬胶囊后为4.1±0.85小时。体外溶出特性较慢的缓释制剂在体内的溶出也较慢，但与酮洛芬胶囊相比，其生物利用度仅为65%。服用酮洛芬胶囊后0至6小时期间，观察到游离酮洛芬的消除程度不成比例地大幅增加。这一结果可以用酮洛芬代谢为其葡糖醛酸苷的饱和机制来解释。然而，由于游离酮洛芬的肾排泄不是酮洛芬消除的主要途径，该参数的相对较大变化不会显著改变消除半衰期或血浆酮洛芬浓度-时间曲线下面积。因此，这种机制的临床意义可能微不足道。
