Shin Dongseong, Lee Sook Joung, Ha Yu-Mi, Choi Young-Sim, Kim Jae-Won, Park Se-Rin, Park Min Kyu
Clinical Trials Center, Gachon University Gil Medical Center, Incheon.
Department of Rehabilitation Medicine.
Drug Des Devel Ther. 2017 Jan 4;11:135-141. doi: 10.2147/DDDT.S121633. eCollection 2017.
Prostaglandin E (PGE) synthesis is modulated by COX2. Changes in PGE could be used to quantify the COX2 inhibition after ibuprofen administration. This study investigated the pharmacokinetic and pharmacodynamic relationships for COX2 inhibition according to three formulations of ibuprofen in healthy male subjects.
A randomized, open-label, single-dose, three-treatment, six-sequence crossover study was performed in 36 healthy South Korean male volunteers. Enrolled subjects received the following three 200 mg ibuprofen formulations: ibuprofen arginine, solubilized ibuprofen capsule, and standard ibuprofen. Pharmacokinetic and pharmacodynamic blood samples were collected for 16 hours following treatment. For pharmacodynamic evaluations, lipopolysaccharide (LPS)-induced PGE inhibition at each time point compared to predose was measured. Noncompartmental analysis was used for pharmacokinetic assessment, and time-weighted average inhibition (WAI) of PGE was applied to the pharmacodynamic evaluation.
After a single oral dose of the ibuprofen formulations, the median times to maximum concentration were 0.42, 0.5, and 1.25 hours in ibuprofen arginine, solubilized ibuprofen capsule, and ibuprofen, respectively. The maximum observed plasma concentration was lower in ibuprofen, and the area under the plasma concentration-time curve was comparable among the three formulations. A significant difference was observed between fast-acting formulations and standard ibuprofen tablets for both maximum concentration and time taken to reach it. Individual formulations had an effect on PGE WAI during the 8 hours following treatment, resulting in significantly lower WAI in standard ibuprofen: ibuprofen arginine 18.4%, solubilized ibuprofen capsule 18.4%, and standard ibuprofen 11.6%.
Rapid absorption and higher peak concentration were observed in ibuprofen arginine and the solubilized ibuprofen capsule. Additionally, fast-acting formulations had more predominant inhibitory activity on the COX2 enzyme.
前列腺素E（PGE）的合成受COX2调节。PGE的变化可用于量化布洛芬给药后COX2的抑制情况。本研究在健康男性受试者中调查了三种布洛芬制剂对COX2抑制的药代动力学和药效学关系。
对36名健康韩国男性志愿者进行了一项随机、开放标签、单剂量、三治疗、六序列交叉研究。入选受试者接受以下三种200mg布洛芬制剂：精氨酸布洛芬、布洛芬软胶囊和标准布洛芬。治疗后16小时采集药代动力学和药效学血样。对于药效学评估，测量每个时间点与给药前相比脂多糖（LPS）诱导的PGE抑制情况。采用非房室分析进行药代动力学评估，并将PGE的时间加权平均抑制率（WAI）应用于药效学评估。
单次口服布洛芬制剂后，精氨酸布洛芬、布洛芬软胶囊和布洛芬的达峰中位时间分别为0.42小时、0.5小时和1.25小时。布洛芬的最大观察血浆浓度较低，三种制剂的血浆浓度-时间曲线下面积相当。速效制剂与标准布洛芬片在最大浓度及其达峰时间上均存在显著差异。各制剂在治疗后8小时内对PGE的WAI有影响，标准布洛芬的WAI显著较低：精氨酸布洛芬为18.4%，布洛芬软胶囊为18.4%，标准布洛芬为11.6%。
精氨酸布洛芬和布洛芬软胶囊吸收迅速且峰值浓度较高。此外，速效制剂对COX2酶具有更显著的抑制活性。
