Variability of Histamine Pharmacodynamic Response in Children With Allergic Rhinitis
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 (r2 = 0.86) than the entire cohort (r2 = 0.64). These data demonstrate a hyper‐responsive histamine phenotype via HILD. This finding is important to future pharmacologic studies of antihistamines.
Jones, B. L.,
Kearns, G. L.,
Neville, K. A.,
Sherwin, C. M.,
Spigarelli, M. G.,
& Leeder, S.
(2013). Variability of Histamine Pharmacodynamic Response in Children With Allergic Rhinitis. The Journal of Clinical Pharmacology, 53 (7), 731-737.