首页> 外文期刊>British Journal of Clinical Pharmacology >Pharmacokinetics and pharmacodynamics of intravenous and inhaled fluticasone furoate in healthy Caucasian and East Asian subjects
【24h】

Pharmacokinetics and pharmacodynamics of intravenous and inhaled fluticasone furoate in healthy Caucasian and East Asian subjects

机译:静脉和吸入糠酸氟替卡松在健康的白种人和东亚受试者中的药代动力学和药效学

获取原文
获取原文并翻译 | 示例
       

摘要

Aim The aim of the study was to evaluate the pharmacokinetics (PK) of inhaled and intravenous (i.v.) fluticasone furoate (FF) in healthy Caucasian, Chinese, Japanese and Korean subjects. Method This was an open label, randomized, two way crossover study in healthy Caucasian, Chinese, Japanese and Korean subjects (n = 20 per group). Inhaled FF (200?μg for 7 days, then 800?μg for 7 days from a dry powder inhaler [DPI]) was administered in one treatment period and i.v.FF (250mug infusion) in the other. FF PK and serum cortisol (inhaled 200?μg only) were compared between the ethnic groups using analysis of variance. P450 CYP3A4 activity and safety were also assessed. Results Ethnic differences in i.v. FF PK were accounted for by body weight differences. CYP3A4 activity was similar across the groups. Higher FF systemic exposure was seen following inhaled dosing in Chinese, Japanese and Korean subjects compared with Caucasian subjects. Absolute bioavailability was greater (36%–55%) in all East Asian groups than for Caucasian subjects following inhaled FF 800?μg. Deconvolution analysis suggested inhaled FF resided in the lung of East Asian subjects longer than for Caucasians (time for 90% to be absorbed [t90]: 29.1–30.8?h vs. 21.4?h). In vitro simulation method predicted comparable delivered lung dose across ethnic groups. Serum cortisol weighted mean was similar between Caucasians and Chinese or Koreans, while in Japanese was on average 22% lower than in Caucasians. All FF treatments were safe and well tolerated. Conclusion Modestly higher (<50%) FF systemic exposure seen in East Asian subjects following inhaled dosing was not associated with a clinically significant effect on serum cortisol, suggesting that a clinical dose adjustment in East Asian subjects is not required.
机译:目的该研究的目的是评估在健康的高加索人,中国人,日本人和韩国人中吸入和静脉内(i.v.)氟替卡松糠酸酯(FF)的药代动力学(PK)。方法这是一项开放标签,随机,双向交叉研究,对象是健康的白种人,中国人,日本人和韩国人(每组n = 20)。在一个治疗期间内给予吸入性FF(200μg,7天,然后从干粉吸入器[DPI]中吸入800μg,7天),在另一个治疗期内给予i.v.FF(250mug输液)。使用方差分析比较了不同种族之间的FF PK和血清皮质醇(仅吸入200?μg)。还评估了P450 CYP3A4的活性和安全性。结果i.v.中的种族差异FF PK是由体重差异引起的。 CYP3A4活性在各组间相似。与白种人受试者相比,在中国,日本和韩国受试者中吸入给药后观察到较高的FF全身暴露。吸入FF800μg后,所有东亚组的绝对生物利用度均比白种人受试者高(36%–55%)。反卷积分析表明,吸入的FF在东亚受试者的肺部驻留的时间比白种人长(90%的吸收时间[t90]:29.1–30.8?h vs. 21.4?h)。体外模拟方法预测了跨种族的可比较的递送肺剂量。高加索人,中国人或韩国人的血清皮质醇加权平均数相似,而日本人的平均水平比高加索人低22%。所有FF治疗均安全且耐受良好。结论吸入给药后在东亚受试者中观察到的适度较高(<50%)FF全身暴露与对血清皮质醇的临床显着影响无关,这表明在东亚受试者中无需临床剂量调整。

著录项

相似文献

  • 外文文献
  • 中文文献
  • 专利
获取原文

客服邮箱:kefu@zhangqiaokeyan.com

京公网安备:11010802029741号 ICP备案号:京ICP备15016152号-6 六维联合信息科技 (北京) 有限公司©版权所有
  • 客服微信

  • 服务号