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J Clin Pharmacol ; 53(7): 731-7, 2013 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-23681823

RESUMO

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.


Assuntos
Antialérgicos/administração & dosagem , Antialérgicos/farmacocinética , Histamina/administração & dosagem , Histamina/farmacocinética , Rinite Alérgica Perene/tratamento farmacológico , Rinite Alérgica Perene/metabolismo , Adolescente , Área Sob a Curva , Criança , Feminino , Humanos , Iontoforese , Fluxometria por Laser-Doppler/métodos , Masculino , Rinite Alérgica
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