STP Position Paper: Interpreting the Significance of Increased Alveolar Macrophages in Rodents Following Inhalation of Pharmaceutical Materials

被引：34

作者：

Nikula, Kristen J. ^{[1
]}

McCartney, Jeffrey E. ^{[2
]}

McGovern, Timothy ^{[3
]}

Miller, Glen K. ^{[4
]}

Odin, Marielle ^{[5
]}

Pino, Michael V. ^{[6
]}

Reed, Matthew D. ^{[7
]}

机构：

[1] Seventh Wave Labs LLC, Chesterfield, MO 63005 USA

[2] Charles River Labs, Senneville, PQ, Canada

[3] SciLucent LLC, Herndon, VA USA

[4] Merck & Co Inc, West Point, PA USA

[5] Roche Diagnost GmbH, Pharma Res & Early Dev, Penzberg, Germany

[6] Sanofi, Bridgewater, NJ USA

[7] Lovelace Resp Res Inst, Albuquerque, NM USA

来源：

TOXICOLOGIC PATHOLOGY | 2014年 / 42卷 / 03期

关键词：

drug development; inhalation; lung; preclinical safety assessment; risk assessment; risk management; pulmonary; SUBCHRONIC INHALATION; INCIDENTAL FINDINGS; LUNG; RATS; RESPONSES; TOXICITY; HISTOPATHOLOGY; CLEARANCE; KINETICS;

D O I：

10.1177/0192623313507003

中图分类号：

R36 [病理学];

学科分类号：

100104 ;

摘要：

The Scientific and Regulatory Policy Committee of the Society of Toxicologic Pathology (STP) appointed a working group to address risk assessment for increases in alveolar macrophages following inhalation of pharmaceutical materials. This position paper provides recommendations for inhalation study-specific terminology and interpretation based on literature and information from marketed inhaled drugs. Based on a weight-of-the-evidence approach, and with appropriate consideration of the physical and pharmacological characteristics of the compound, uncomplicated increases in the size or number of alveolar macrophages in nonclinical species are interpreted as nonadverse.

引用

页码：472 / 486

页数：15