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J Clin Pharmacol. 2013 Jul;53(7):731-7. doi: 10.1002/jcph.93. Epub 2013 May 16.

Variability of histamine pharmacodynamic response in children with allergic rhinitis.

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Department of Paediatrics, University of Missouri, Kansas City, MO 64108, USA.


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.

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