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Pharmacokinetic equivalence of pediatric dosages of desloratadine syrup in children and standard 5-mg desloratadine tablets in adults

2002; Elsevier BV; Volume: 109; Issue: 1 Linguagem: Inglês

10.1016/s0091-6749(02)81414-2

1097-6825

Christopher Banfield, Samir K. Gupta, Melton B. Affrime, Vijay Batra,

Drug-Induced Adverse Reactions

CONCLUSIONS: Fexofenadine rapidly reduced the symptoms of nasal congestion in PAR, and this effect was maintained throughout the 4week study period. This early effect may reflect the anti-allergic activity of fexofenadine, as nasal congestion is a symptom caused by allergic inflammation. This pilot study supports the clinical efficacy of fexofenadine in PAR, and provides further evidence of its efficacy in the management of nasal congestion. 2 7 R Pharmacokinetic Equivalence of Pediatric Dosages of DesloI 1 , 1 ratadine Syrup in Children and Standard 5-mg Desloratadine Tablets in Adults Christopher Banfield, Samir Gupta, Melton Affrime, Vijay Batra Schering Plough, Kenilworth, NJ Desloratadine (DL), a novel, nonsedating Hi-receptor antagonist, has previously demonstrated safety and efficacy in adult patients with seasonal allergic rhinitis and chronic idiopathic urticaria. In these studies, the pharmacokinetic profiles of 1.25-rag and 2.5-mg doses of DL syrup were evaluated in children 2-5 and 6-11 years of age, respectively, and compared with values obtained in adults receiving a standard 5-mg DL tablet. Two openlabel, single-dose trials (N = 18 for each) of DL syrup (0.5 mg/mL) were conducted in healthy male and female children. As in previous adult trials, blood samples were collected prior to drug administration and at ten prespecified time points over the course of 96 hours; AUC (from time 0 to the final measurable sampling time) and Cma x values were calculated for DL and its metabolite, 3-OH DL. Subjects were carefully monitored and questioned throughout the study for possible adverse events. A thorough physical examination, ECG, and clinical laboratory tests were performed upon entry and at study completion. The 1.25-rag and 2.5-mg doses of DL syrup produced pharmacokinetic values similar to those observed previously in adults administered a standard 5-mg DL tablet. The mean AUC and Cma x values for the 1.25 mg/2-5 y and 2.5 mg/6-11 y groups were 42.0 ng.hr/mL and 2.68 ng/mL, and 48.6 ng.hr/mL and 2.23 ng/mL, respectively. The corresponding mean values in adults receiving a 5-mg DL tablet were 45.8 ng.hr/mL and 2.44 ng/mL. Mean 3-OH DL pharmacokinetic values were also comparable between adults and each group of children. Desloratadine was safe and well tolerated in both age groups. No adverse events were reported. These studies demonstrate that 1.25-mg and 2.5-mg doses of DL syrup in children 2-5 and 6-11 years of age, respectively, produce a comparable degree of drug exposure to that observed in adults receiving the recommended 5-mg dose of DL. The pharmacokinetic equivalence of the adult and pediatric doses suggests that the efficacy and safety of DL may be comparable in pediatric and adult populations. 7 Q Fixed-Dose Desloratadine and Pseudoephedrine Relieves Mod/ ~ erate/Severe Nasal Congestion in Patients With Seasonal Allergic Rhinitis Eric Schenkel*, Jonathan Corren§, JJ Murray¥ *Valley Clinical Research Center, Easton, PA §Allergy Research Foundation Incorporated, Los Angeles, CA ¥Vanderbilt University, Nashville, TN Nasal congestion, the most bothersome symptom of seasonal allergic rhinitis (SAR) for many patients, typically responds poorly to antihistamines. Previous clinical studies, however, have suggested that desloratadine (DL), a next-generation, nonsedating HI-receptor antagonist, possesses intrinsic decongestant activity. While DL alone has been shown to effectively treat mild/moderate nasal congestion in patients with SAR, more severe congestion may require pseudoephedrine (PSE). The efficacy of a DL/PSE combination tablet was investigated in a multicenter, randomized, parallel-group, double-blind study, conducted during the fall allergy season, to determine if a therapeutic advantage was conferred to patients with moderate/severe congestion. Patients enrolled were aged 12-78 years with a minimum 2-year history of SAR and at least moderate nasal congestion at baseline, in addition to other SAR symptoms. Patients received DL/PSE 5/240 mg (n = 336) combination tablet, DL 5 mg (n = 340), or PSE 240 mg (n = 342) once each morning for 15 days. The severity of nasal congestion was measured using a 4-point scale (0 = none to 3 = severe). Scores were recorded every am and pm, to assess how patients felt over the previous 12 hours (reflective score). At baseline, the average congestion score for all groups was at least 2.54 (maximum = 3), indicating patients suffered from moderate/severe congestion. The effect of treatment on nasal congestion was measured as change from baseline in mean am/pro reflective nasal congestion score. Compared with DL (~).65) or PSE (~).70) alone, the DL/PSE combination tablet was significantly superior in reducing nasal congestion (~).85) over the entire 2-week study period (DL/PSE vs DL, P 0.05). Sneezing score was significantly lower in patients treated with loratadine and montelukast, cetirizine and montelukast, and cetirizine alone. We may conclude that 6 week pre-treatment with cetirizine and montelukast provides the most effective prevention of allergic rhinitis symptoms. Group 1 Group 2 Group 3 Group 4 Group 5 Congestion 1.05 +/0.07 0.95 +/0.07 1.00 +/0.06 1.00 +/0.06 0.52 +/0.05 Rhinorrhea 0.62 +/0.07 0.84 +/0.07 1.62 +/0.10 1.08 +/0.06 0.31 +/0.04 Itching 0.75 +/0.06 0.35 +/0.05 1.62 +/0.08 0.56 +/0.05 0.43 +/0.09 Sneezing 0.94+/-0.06 1.59+/-0.10 1.50+/-0.08 0.89+/-0.06 0.87+/-0.06