<b>ヒト初回投与試験の開始用量に関するレトロスペクティブ研究 </b>

• 佐藤 彰秀

  北里大学大学院薬学研究科臨床医学（医薬開発学） 中外製薬株式会社プロジェクト推進部

• 成川 衛

  北里大学大学院薬学研究科臨床医学（医薬開発学）

書誌事項

タイトル別名

• <b>Retrospective Study for Determination of the Starting Dose in First-in-Human Clinical Studies </b>

抄録

We conducted a retrospective study to review the no-observed-adverse-effect levels (NOAEL) in nonclinical studies and the first-human-doses (FHD) in first-in-human (FIH) studies, and to investigate the safety factors used in past FIH studies. In addition, we examined several potential factors that may influence the dose setting. Ethical drugs containing a new chemical entity approved in Japan from 2008 to 2012 were included in the present study. A human-equivalent dose of NOAEL (NHD) was calculated from NOAEL obtained from toxicity studies, based on the body surface area. The ratio of NHD to FHD was defined as the “FHD index” in this study, which was a synonym of safety factor based on body surface area. Drugs in the following categories were excluded from the study: biopharmaceuticals, derivatives of existing drug (including prodrug, active metabolite, and optical isomer), historically established medicines, combination drugs, topical application drugs, and general anaesthesia and relative medicines. In many therapeutic areas other than oncology, the safety factor to determine the starting dose in FIH studies was greater than 10, which was recommended by FDA guidance document. This finding suggested that the starting doses had been determined very prudently in past FIH studies. No apparent differences in FHD index were observed with respect to administration route (oral versus injection), subject population in FIH study (Japanese versus non-Japanese), and the most sensitive species in toxicity studies. No apparent relationship between the FHD index and the quantity of species-difference in NOAEL was identified in this study.

収録刊行物

• 臨床薬理

  臨床薬理 46 (2), 65-70, 2015

  一般社団法人 日本臨床薬理学会

キーワード

• first-in-human studies
• human equivalent doses
• no observed adverse effect levels
• safety factors
• starting dose determinations

詳細情報

• CRID: 1390001205368096640
• NII論文ID: 130005064871
• DOI: 10.3999/jscpt.46.65
• ISSN: 18828272
• ISSN: 03881601
• Web Site: https://search.jamas.or.jp/link/ui/2015361823
• 本文言語コード: ja
• データソース種別:
  • JaLC
  • Crossref
  • CiNii Articles
• 抄録ライセンスフラグ: 使用不可