Addendum al Consenso Nacional de Rinitis Alérgica en Pediatría: Incorporación de nuevos conceptos Translated title: Addendum to the National Consensus on Allergic Rhinitis in children: incorporation of new concepts

A new classification of allergic rhinitis (AR) has been proposed by the allergic rhinitis and its impact on asthma (ARIA) workgroup. The validity of this new classification is still largely unknown, especially the extent to which it differs from the classical seasonal/perennial (SAR/PAR) classification, and how and whether intermittent and persistent types of AR, as defined by ARIA, differ from each other. Two-step cross-sectional, population-based, in six Western Europe countries; telephone interview followed by clinical diagnosis [including specific immunoglobulin E (IgE) measurements] in a selected subset. Within the population with AR, 29% of the subjects had persistent AR. There was no association between the intermittent/persistent and the SAR/PAR classifications. Subjects with persistent AR had more severe symptoms, and higher rate of self-awareness and previous diagnosis of AR; they were also clearly distinct in their sensitization pattern and medication use. The classic types of SAR/PAR cannot be used interchangeably with the new classification of intermittent/persistent, as they do not represent the same stratum of disease. There is also evidence that the persistent type describes a distinct group with characteristics that differentiates them from intermittent AR. These results support the validity of the new ARIA classification.

Developmental changes during infancy and childhood can affect drug pharmacokinetics (PK), i.e., absorption, distribution, metabolism, and renal excretion. This, in turn, influences optimal dosing, efficacy, and safety. To date, of the 40 H1-antihistamines available worldwide, only 11 have been studied in children using a PK approach. Here, we provide the pediatricians' perspective on the population PK of levocetirizine, the pharmacologically active enantiomer of cetirizine, in very young children who received oral cetirizine, and describe the factors that influence levocetirizine PK in this population. In a prospective, randomized, double-blind, parallel-group, placebo-controlled study, very young children received oral cetirizine 0.25 mg/kg twice daily for 18 months. Plasma levocetirizine concentrations were measured in timed, sparse blood samples collected at steady-state (3, 12 and 18 months after commencement of treatment) for the purpose of monitoring safety, and levocetirizine population, PK parameters were derived by using non-linear mixed effects modeling. In 343 children (age 14-46 months, body weight 8.2-20.5 kg), a total of 943 blood samples were obtained. Compliance with cetirizine dosing was documented. The population PK model used predicted that with increasing body weight, levocetirizine oral clearance would increase by 0.044 l/h/kg, and levocetirizine volume of distribution would increase by 0.639 l/kg. Levocetirizine PK were not influenced by eosinophilia, sensitization to allergens, allergic disease, gastroenteritis/diarrhea, or concomitant ingestion of other medications. This population PK model predicts that in very young children, the oral clearance of levocetirizine will be rapid and will increase as body weight and age increase, therefore, levocetirizine dosing should be based on body weight and age in this population. Compared with older patients, on a mg/kg basis, relatively higher doses may be needed, and twice-daily dosing may be necessary, as previously reported for the related racemic H1-antihistamine cetirizine.