高加索人和日本人健康参与者的食物效应和药代动力学桥接作用

IF 1.5 4区 医学 Q3 PHARMACOLOGY & PHARMACY Clinical Pharmacology in Drug Development Pub Date : 2024-07-11 DOI:10.1002/cpdd.1436
Shichang Miao, Pirow Bekker, Danielle Armas, Mary Lor, Ryuzo Hanada, Shota Okamura, Yuko Umezawa, Ashit Trivedi
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引用次数: 0

摘要

阿伐潘 30 毫克,每日两次(BID),已被批准用于治疗严重的活动性抗中性粒细胞胞浆自身抗体相关性血管炎(肉芽肿伴多血管炎和显微镜下多血管炎)。通过两项涉及健康成年参与者的 1 期研究,考察了食物对日本参与者体内阿伐戈班药代动力学(PKs)和 PK 桥接的影响。研究 1 是一项开放标签、交叉试验,参与者在禁食和进食条件下口服单次 30 毫克剂量的阿伐戈班。研究 2 是一项随机、单盲、安慰剂对照试验,参加者为白种人和日本人:A 部分研究了在空腹和进食条件下单次服用 10 毫克和 30 毫克阿伐戈班的情况,B 部分研究了 30 毫克和 50 毫克阿伐戈班(每日两次)的情况。日本参试者在禁食条件下单次服用 10 毫克和 30 毫克的 PK 与白种人参试者的 PK 进行了比较。食物使阿伐戈班血浆浓度-时间曲线下从时间 0 到时间无穷大的面积(AUC0-inf)大幅增加了 1.72 倍,这支持了与食物同时服用阿伐戈班的建议。最大血浆浓度(Cmax)保持相对不变。达到 Cmax 的中位时间(tmax)延迟了 3 小时。食物对活性代谢物 CCX168-M1(M1)的 AUC 没有明显影响。阿伐潘和 M1 的暴露量为
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Food Effect and Pharmacokinetic Bridging of Avacopan in Caucasian and Japanese Healthy Participants

Avacopan 30 mg twice daily (BID) is approved for the treatment of severe active antineutrophil cytoplasmic autoantibody–associated vasculitis (granulomatosis with polyangiitis and microscopic polyangiitis). Food effect on avacopan pharmacokinetics (PKs) and PK bridging in Japanese participants were examined through 2 phase 1 studies involving healthy adult participants. In Study 1, an open-label, crossover trial, participants received oral administration of a single 30-mg dose of avacopan under fasted and fed conditions. Study 2 was a randomized, single-blind, placebo-controlled trial in Caucasian and Japanese participants: Part A investigated single doses of 10 and 30 mg of avacopan under fasted and fed conditions and Part B investigated 30 and 50 mg BID avacopan. The PKs of single-dose administrations of 10 and 30 mg in Japanese participants was compared with that in Caucasian participants under fasted conditions. Food substantially increased plasma avacopan area under the plasma concentration-time curve from time 0 to time infinity (AUC0-inf) by 1.72-fold, supporting the recommendation of taking avacopan with food. Maximum plasma concentration (Cmax) remained relatively unchanged. The median time to reach Cmax (tmax) was delayed by 3 hours. No significant food effect was observed on the active metabolite CCX168-M1 (M1) AUC. Avacopan and M1 exposures were <1.5-fold higher in Japanese participants than in Caucasian participants following multiple-dose administration of avacopan.

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来源期刊
CiteScore
3.70
自引率
10.00%
发文量
154
期刊介绍: Clinical Pharmacology in Drug Development is an international, peer-reviewed, online publication focused on publishing high-quality clinical pharmacology studies in drug development which are primarily (but not exclusively) performed in early development phases in healthy subjects.
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