The Reliability of Histamine Pharmacodynamic Response Phenotype Classification in Children With Allergic Disease

Frontiers in Pharmacology

Catherine M. Sherwin¹  Bridgette L. Jones²  Xiaoxi Liu⁵  Shaun S. Kumar⁵ 

[1] Department of Pediatrics, Dayton Children’s Hospital, Wright State University Boonshoft School of Medicine, Dayton, OH, United States;Department of Pediatrics, University of Missouri, Kansas City, MO, United States;Department of Pharmacotherapy, College of Pharmacy, University of Utah, Salt Lake City, UT, United States;Division of Allergy, Asthma, Clinical Immunology, Children’s Mercy Hospital, Kansas City, MO, United States;Division of Clinical Pharmacology, Department of Pediatrics, University of Utah School of Medicine, Salt Lake City, UT, United States;Division of Pediatric Pharmacology, Therapeutic Innovation, Children’s Mercy Hospital, Kansas City, MO, United States;

关键词: histamine;    children;    pharmacodynamics;    allergy;    phenotype;   

DOI  :  10.3389/fphar.2020.00227

来源: DOAJ

【 摘 要 】

We have identified distinct histamine pharmacodynamic response phenotypes in children with allergic disease utilizing histamine iontophoresis with laser Doppler (HILD). These response phenotypes may be relevant in guiding therapeutic decision making for agents targeting the allergic response pathways. However, the reliability of these response phenotypes has not been assessed. Therefore, we performed HILD in children with allergic rhinitis and/or asthma on two to three separate occasions. HILD response-time data were analyzed in NONMEM using a linked effect PKPD model. Examination of observed vs. classified response phenotypes predicted response plots and the sum of residuals. The intraclass correlation coefficient (ICC) was used to determine the reliability of phenotype classification. Eighty-two percent of children exhibited a reliable histamine response phenotype [intraclass correlation coefficient 0.77 (95% CI 0.44–0.93]. These preliminary results suggest moderate reliability of HILD response phenotype in children. Further exploration is needed to determine contributions to phenotype variability.

【 授权许可】

Unknown