RESUMEN
OBJECTIVE: Pharmacodynamic studies have demonstrated that levocetirizine is the active enantiomer of cetirizine. This first therapeutic trial of levocetirizine aimed at determining the dosage with the best benefit/risk ratio in patients with seasonal allergic rhinitis (SAR). METHODS: Patients with seasonal allergic rhinitis were randomised in a placebo-controlled, double-blind, parallel-group multicentre study 2.5, 5, 10 mg levocetirizine or placebo once daily during 2 weeks. Patients filled in a diary evaluation card every evening before taking study medication using the classical (0-3) scale for assessment of severity of sneezing, rhinorrhea, nasal congestion, nasal pruritus and ocular pruritus over the preceding 24 hours. The Total Four-Symptom Score (T4SS) was calculated by adding the individual symptom scores, excluding nasal congestion. RESULTS: 470 patients were included and constituted the intent-to-treat population. All 3 doses of levocetirizine were significantly superior to placebo in reducing the mean T4SS over the 2 weeks (all P (0.001). Additionally, individual symptom severity scores for sneezing, rhinorrhea, itchy nose, and itchy eyes were also significantly decreased for all doses of levocetirizine. Levocetirizine was significantly superior to placebo in reducing symptom severity with an important global treatment effect (P = 0.0001), except for nasal congestion. Furthermore, there was simple linear relationship between levocetirizine dosages and reduction of T4SS (P = 0.001). All doses were well tolerated, somnolence was higher with 10 mg (10.2%) than 5 mg (1.7%) and other adverse events were more frequent with the highest dose. CONCLUSION: Levocetirizine 5 mg once daily has an optimal benefit/risk ratio in the treatment of SAR.
Asunto(s)
Cetirizina/uso terapéutico , Antagonistas de los Receptores Histamínicos H1/uso terapéutico , Rinitis Alérgica Estacional/tratamiento farmacológico , Adulto , Cetirizina/administración & dosificación , Método Doble Ciego , Esquema de Medicación , Femenino , Antagonistas de los Receptores Histamínicos H1/administración & dosificación , Humanos , Masculino , Rinitis Alérgica Estacional/diagnóstico , SeguridadRESUMEN
We compared the efficacy and safety of cetirizine (5 mg), pseudoephedrine retard (120 mg), and the combination of cetirizine (5 mg) with pseudoephedrine retard (120 mg), each given twice daily for two weeks to subjects with pollen-associated allergic rhinitis. The study was multicentre and of randomized, double-blind, parallel-group design. Five rhinitis symptoms were rated according to severity on a scale of 0 - 3, daily by patients and at each clinic visit by investigators. A total of 687 patients, aged 9 - 66 years (mean: 32 years) was randomised to treatment (cetirizine: 231; pseudoephedrine: 226; combination: 230). On entry, the three groups were comparable in relevant respects. The primary outcome measure was based on the five symptoms assessed by the patients over the 2-week treatment period. The combination was more effective, providing at least 20% more "comfortable days" (symptoms absent or at most mild) than cetirizine or pseudoephedrine given alone (median values: 53.3%, 30.8%, and 33.3%, respectively; p < 0.001). For nasal obstruction, the combination (mean score: 1.19) was more effective than cetirizine (mean score: 1.43; p = 0.0005), but there was little difference between the combination and pseudoephedrine (mean score: 1.22; not significant). Sneezing, rhinorrhoea, nasal and ocular pruritus were better controlled by combination (mean 4-symptom score: 0.77) than by pseudoephedrine alone (mean 4-symptom score: 1.12; p < 0.001) and also better than by cetirizine alone (mean 4-symptom score: 0.93; p < 0.001). No unexpected adverse reactions were observed. A combination of cetirizine and pseudoephedrine retard is well tolerated and superior to each given alone for moderate to severe allergic seasonal rhinitis, especially when nasal obstruction is a predominant symptom.
Asunto(s)
Broncodilatadores/administración & dosificación , Cetirizina/administración & dosificación , Efedrina/administración & dosificación , Antagonistas de los Receptores Histamínicos H1/administración & dosificación , Rinitis Alérgica Perenne/tratamiento farmacológico , Adolescente , Adulto , Análisis de Varianza , Broncodilatadores/efectos adversos , Cetirizina/efectos adversos , Niño , Preparaciones de Acción Retardada , Método Doble Ciego , Quimioterapia Combinada , Efedrina/efectos adversos , Femenino , Antagonistas de los Receptores Histamínicos H1/efectos adversos , Humanos , Masculino , Persona de Mediana Edad , Estadísticas no ParamétricasRESUMEN
Eight children (3.84 +/- 1.17 years old) received a single oral 5 mg cetirizine dose (0.32 +/- 0.07 mg.kg-1) as a 10 mg.ml-1 solution, 1.73 (+/- 0.64) hours before a minor surgical intervention (mean duration +/- SD = 0.90 +/- 0.25 h). Seven venous blood samples were collected before administration (t0) and 0.5 h, 1.5 h, 4 h, 8 h, 12 h and 24 h after dosing, and urine samples were collected up to 24 hours after the dose. The mean +/- SD kinetic parameters were: peak plasma level (Cmax) 607 +/- 231 micrograms.l-1 reached in 1.93 +/- 1.39 h (tmax), elimination half-life (t1/2) 5.55 +/- 0.98 h, area under the plasma concentration time curve (AUC0-infinity) 4,772.1 +/- 1,318.4 micrograms.l-1.h, mean residence time (MRT) 8.13 +/- 1.31 h, apparent plasma clearance (Cl/f) 1.27 +/- 0.80 ml.min-1.kg-1, apparent volume of distribution (Vz/f) 0.60 +/- 0.38 l.kg-1. Urinary recovery was 38.4 +/- 9.9% (n = 4) of the dose. Renal clearance was 0.42 +/- 0.10 ml.min-1.kg-1 (n = 6). No influence of age on the cetirizine parameters was evidenced among this group, except for MRT (p < 0.05) which decreases with age. When compared with results in adults, elimination half-life (t1/2) was twice as short and apparent clearance twice as great. These results suggest that a higher dosage b.i.d. may be required in children.