Nayak R K, Ng K T, Gottlieb S, Plostnieks J
Clin Pharmacol Ther. 1980 Mar;27(3):395-401. doi: 10.1038/clpt.1980.53.
Kinetics of zomepirac, an oral, nonnarcotic analgesic, were studied in healthy males in 3 clinical experiments. In study A, zomepirac 100 mg was taken as tablet, capsule, and solution. Bioavailability of zomepirac from the 3 dosage forms was much the same. Zomepirac absorption was rapid, peak plasma concentrations being reached within 1 to 1 hr. Plasma concentration profile could be described by the 2-compartmentoral absorption model with an absorption rate constant (Ka) of 7.66 hr-1 t 1/2 = 0.09 hr), a rapid disposition rate constant (alpha) of 0.75 hr-1 (t 1/2 = 0.94 hr), and a slow disposition rate constant (beta) of 0.16 hr-1 (t 1/2 = 4.3 hr). In study B, safety and acceptability were established with 100 mg 4 times a day for 14 days followed by 150 mg 4 times a day for 14 days. Zomepirac plasma levels indicated attainment of steady state within less than 3 days of treatment. There was little drug accumulation on the regimens studied. There was no change in plasma kinetics after 14 days on either regimen. In study C, dose/bioavailability response was followed at 50-, 100-, and 200-mg dose levels. There were linear correlations between dose and peak plasma concentration, area under the plasma concentration-time curve, and urinary excretion of intact and total (intact + glucuronide conjugate) zomepirac during the 12 hr following drug administration.
在3项临床试验中，对口服非麻醉性镇痛药佐美酸的动力学进行了研究，试验对象为健康男性。在研究A中，服用了100毫克佐美酸的片剂、胶囊和溶液。这3种剂型的佐美酸生物利用度大致相同。佐美酸吸收迅速，1至1.5小时内达到血浆峰浓度。血浆浓度曲线可用二房室口服吸收模型描述，吸收速率常数（Ka）为7.66小时-1（t 1/2 = 0.09小时），快速处置速率常数（α）为0.75小时-1（t 1/2 = 0.94小时），缓慢处置速率常数（β）为0.16小时-1（t 1/2 = 4.3小时）。在研究B中，确定了安全性和可接受性，即每天4次，每次100毫克，服用14天，随后每天4次，每次150毫克，服用14天。佐美酸血浆水平表明，治疗不到3天即可达到稳态。在所研究的给药方案中几乎没有药物蓄积。两种给药方案用药14天后血浆动力学均无变化。在研究C中，在50、100和200毫克剂量水平下观察了剂量/生物利用度反应。给药后12小时内，剂量与血浆峰浓度、血浆浓度-时间曲线下面积以及完整的和总的（完整的+葡萄糖醛酸结合物）佐美酸尿排泄之间存在线性相关性。
