Pharmacokinetics, safety and tolerability of mipomersen in healthy Japanese volunteers and comparison with Western subjects

耐受性 医学 药代动力学 最大值 人口 安慰剂 内科学 不利影响 胃肠病学 环境卫生 病理 替代医学
作者
Zhaoyang Li,Marjie Hard,Grit Andersen,G Pabst,Gilbert Wagener,Tejdip Singh,Wai Chin,Kerry Culm-Merdek,Ingrid Boltje,Lisa L. von Moltke
出处
期刊:International Journal of Clinical Pharmacology and Therapeutics [Dustri-Verlag Dr. Karl Feistle]
卷期号:52 (04): 314-320 被引量:5
标识
DOI:10.5414/cp201975
摘要

To characterize the safety, tolerability, pharmacokinetics (PK) and dose proportionality of mipomersen after single subcutaneous (SC) administration to Japanese healthy subjects; and to compare the PK profiles of Japanese and Western subjects.20 healthy first-generation Japanese male subjects were enrolled into one of three treatment cohorts (50, 100 and 200 mg SC) in a dose-escalation design. Within each cohort, subjects were randomized in a 4 : 1 ratio to receive mipomersen or placebo.Mipomersen was absorbed rapidly after SC administration; median tmax varied between 2 and 3 hours. After reaching peak levels, plasma concentrations of mipomersen decayed multiphasically with an initial distribution t1/2 in several hours and a terminal t1/2 of 261 - 393 hours. Mean Cmax increased in a dose-linear manner while all mean AUC from time 0 to different cut points increased slightly more than dose proportionally. Although mean terminal t1/2 varied in the dose range tested, it did not show dose-dependence. The PK profiles of mipomersen in Japanese subjects are similar to those observed in Western subjects. A single SC dose of 50 mg, 100 mg and 200 mg mipomersen was well tolerated by male Japanese subjects.Single SC doses of 50 - 200 mg were safe and well tolerated when administered to Japanese subjects. Comparison of PK between Japanese and Western subjects does not support any need for dose adjustment in Japanese population in future clinical development.
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