Benet L Z
Department of Pharmacy, University of California, San Francisco 94143-0446.
Rheumatol Int. 1993;13(2 Suppl):S3-5. doi: 10.1007/BF00290277.
Etodolac exhibits linear pharmacokinetics, good oral bioavailability, greater than 99% protein binding, a low oral clearance (almost exclusively non-renal), a relatively small volume of distribution and a half-life that averages 7.3 +/- 4.0 h. No significant pharmacokinetic differences have been noted in patients with mild to moderate renal impairment, in patients with cirrhosis, in the elderly or in patients with arthritis. The pharmacodynamics of the drug are well characterized in terms of pain intensity differences (PID) yielding an EC50 of 13 micrograms/ml. The extensive kinetic/dynamic characterization of etodolac, together with its short half-life, makes the drug an ideal candidate for a sustained-release (SR), once-a-day formulation. Etodolac SR formulations exhibit the same pharmacokinetic characteristics as the conventional-release (CR) formulation, except for a longer time to peak concentration and a lower peak concentration. Fluctuation ratios upon multiple dosing are comparable for equal total daily doses of etodolac SR and twice-daily doses of the CR formulation. Administration with food (high-fat meal) did not affect areas under the curve for either the CR or the SR product. Simulation analyses for etodolac SR suggest that PID responses are maintained over 24 h.
依托度酸呈现线性药代动力学，口服生物利用度良好，蛋白结合率大于99%，口服清除率低（几乎完全是非肾清除），分布容积相对较小，半衰期平均为7.3±4.0小时。在轻度至中度肾功能损害患者、肝硬化患者、老年人或关节炎患者中未观察到明显的药代动力学差异。该药物的药效学在疼痛强度差异（PID）方面有很好的特征描述，其半数有效浓度（EC50）为13微克/毫升。依托度酸广泛的动力学/动态特征，以及其较短的半衰期，使其成为每日一次缓释（SR）制剂的理想候选药物。依托度酸SR制剂具有与普通释放（CR）制剂相同的药代动力学特征，只是达峰浓度时间更长，峰浓度更低。对于等量的依托度酸每日总剂量，SR制剂多次给药后的波动比与CR制剂每日两次给药后的波动比相当。与食物（高脂餐）一起给药对CR或SR产品的曲线下面积均无影响。依托度酸SR制剂的模拟分析表明，PID反应可维持24小时。
