title: Variability of histamine pharmacodynamic response in children with allergic rhinitis.
abstract: Histamine iontophoresis with laser Doppler monitoring (HILD) is a robust and dynamic surrogate for histamine microvasculature response. We characterized histamine pharmacodynamics in children using HILD. HILD was performed in 54 children with allergic rhinitis. A non-compartmental analysis and non-linear mixed-effects model with a linked effect PK/PD model was used to provide estimates for area under the effect curve (AUEC), maximal response over baseline (EffmaxNT), and time of EffmaxNT (Tmax). Data were placed in sub-groups by visualization of time vs. response relationships. ANOVA and regression analyses were used for sub-group comparisons. Three histamine response phenotypes were identified. One group demonstrated a hyper-responsive phenotype (higher Tmax, EffmaxNt and AUEC, P < .01). AUEC and EffmaxNT were more strongly associated in this group (r(2)  = 0.86) than the entire cohort (r(2)  = 0.64). These data demonstrate a hyper-responsive histamine phenotype via HILD. This finding is important to future pharmacologic studies of antihistamines.
authors.affiliation: Department of Paediatrics, University of Missouri, Kansas City, MO 64108, USA. bljones@cmh.edu
authors.forename: Bridgette L
authors.initials: BL
authors.lastname: Jones
authors.forename: Gregory
authors.initials: G
authors.lastname: Kearns
authors.forename: Kathleen A
authors.initials: KA
authors.lastname: Neville
authors.forename: Catherine M T
authors.initials: CM
authors.lastname: Sherwin
authors.forename: Michael M G
authors.initials: MM
authors.lastname: Spigarelli
authors.forename: J Steven
authors.initials: JS
authors.lastname: Leeder
mesh_terms: D000293:Adolescent; D018926:Anti-Allergic Agents / Q000008:administration & dosage* / Q000493:pharmacokinetics*; D019540:Area Under Curve; D002648:Child; D005260:Female; D006632:Histamine / Q000008:administration & dosage* / Q000493:pharmacokinetics*; D006801:Humans; D007478:Iontophoresis; D017078:Laser-Doppler Flowmetry / Q000379:methods; D008297:Male; D065631:Rhinitis, Allergic; D012221:Rhinitis, Allergic, Perennial / Q000188:drug therapy* / Q000378:metabolism*
chemical_list: D018926:Anti-Allergic Agents; D006632:Histamine