Department of Clinical Pharmacology and Therapeutics, Seoul National University College of Medicine and Hospital, Seoul, Korea.
Bristol Myers Squibb Company, Summit - West, NJ, USA.
Clin Transl Sci. 2021 Jul;14(4):1505-1511. doi: 10.1111/cts.13013. Epub 2021 May 1.
We performed a two-part study to evaluate the pharmacokinetics, safety, and tolerability of oral apremilast, a phosphodiesterase 4 inhibitor indicated for the treatment of psoriasis, in healthy Korean adult men. In part 1, there were 12 subjects who randomly received a single oral dose of apremilast at 20, 30, or 40 mg in each of 3 periods in a crossover fashion. In part 2, there were 16 subjects who randomly received 30 mg of apremilast or its matching placebo in a ratio of 3:1 twice daily for 14 days. Apremilast was rapidly absorbed (maximum concentration: ~2-3 h postdose), and eliminated according to a monoexponential pattern with a terminal-phase elimination half-life of 8-9 h. The exposure to apremilast increased in a dose-proportional manner and accumulation was 1.6-fold at steady-state. Apremilast was well-tolerated after a single oral administration and multiple oral administrations in Korean adult men; all of the treatment-emergent adverse events were mild and recovered without sequelae. In conclusion, apremilast was safe and well-tolerated in healthy Korean adult men when administered single oral doses of 20, 30, or 40 mg or when administered multiple oral doses of 30 mg b.i.d. for 14 days. Overall exposures increased in an approximate dose proportional manner in healthy Korean adult men.
我们进行了一项两部分的研究,以评估磷酸二酯酶 4 抑制剂阿普米司特(用于治疗银屑病)在健康韩国成年男性中的药代动力学、安全性和耐受性。在第 1 部分中,有 12 名受试者以交叉方式随机接受单次口服 20、30 或 40mg 阿普米司特的单一剂量,每个剂量在 3 个时期进行。在第 2 部分中,有 16 名受试者以 3:1 的比例随机接受 30mg 阿普米司特或其匹配的安慰剂,每日 2 次,持续 14 天。阿普米司特吸收迅速(最大浓度:约 2-3 小时后),根据单指数模式消除,终末半衰期为 8-9 小时。阿普米司特的暴露量呈剂量比例增加,稳态时的蓄积为 1.6 倍。阿普米司特在韩国成年男性单次和多次口服后耐受性良好;所有治疗出现的不良反应均为轻度,且无后遗症恢复。总之,阿普米司特在健康韩国成年男性中单次口服 20、30 或 40mg 或每日口服 30mg 2 次,连续 14 天是安全且耐受良好的。在健康的韩国成年男性中,总体暴露量呈近似剂量比例增加。
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