Effects on growth and tolerance and hypoallergenicity of an amino acid-based formula with synbiotics.

BACKGROUND: To evaluate the effects of an amino acid-based formula (AAF) with synbiotics on growth and tolerance in healthy infants. The hypoallergenicity of this AAF with synbiotics was evaluated in subjects with cow's milk allergy (CMA). METHODS: Study 1: 115 full-term, healthy infants randomly received an AAF with synbiotics or a commercially available AAF for 16 wk. Subjects' weight, length, and head circumference were primary outcome measures. Stool characteristics and gastrointestinal (GI) symptoms were secondary outcome measures. Clinical examinations, dietary intake, clinical laboratory results, and adverse events were recorded. Study 2: hypoallergenicity of the AAF with synbiotics was evaluated in 30 infants and children with immunoglobulin E (IgE)-mediated CMA using a double-blind, placebo-controlled food challenge, and a 7-d feeding period. RESULTS: Study 1: comparable results in growth parameters and tolerance were observed for both groups. Minimal differences were observed in stool characteristics and GI symptoms throughout the study. Study 2: all 30 subjects with IgE-mediated CMA completed the study with no allergic reactions detected to challenges. CONCLUSION: These studies demonstrate that an AAF with synbiotics is safe and well tolerated and promotes normal growth when fed to healthy full-term infants as the sole source of nutrition and is hypoallergenic in subjects with CMA.

The concept of receptor occupancy to predict clinical efficacy: a comparison of second generation H1 antihistamines.

Second generation H1 antihistamines are considered first-line therapy for allergic rhinitis and chronic idiopathic urticaria, largely because of their nonsedating effects. Evaluating pharmacokinetic and pharmacodynamic parameters and clinical efficacy of a drug is important, but models to predict clinical efficacy are lacking. Receptor occupancy (RO), a predictor for human pharmacodynamics and antihistamine potency that takes into account the affinity of the drug for the receptor and its free plasma concentration, may be a more accurate way to predict a drug's clinical efficacy. This study was designed to assess the concept of RO as a surrogate for clinical efficacy, using examples of second generation oral antihistamines. A literature review was conducted using MEDLINE. Search terms included allergy, allergic rhinitis, drug efficacy, over-the-counter drugs, perennial allergic rhinitis, seasonal allergic rhinitis, second generation antihistamines, chronic idiopathic urticaria, and treatment outcomes. Abstracts and posters from recent allergy-related society meetings were also used. RO of several second generation H1 antihistamines was derived from noncomparative and head-to-head studies. Fexofenadine and levocetirizine showed similar RO at 4 hours, both higher than that of desloratadine. Levocetirizine established higher RO than fexofenadine or desloratadine at 12 and 24 hours. RO for these agents appeared to correlate with pharmacodynamic activity in skin wheal and flare studies and with efficacy in allergen challenge chamber studies. Parameters affecting RO included time from dosing, pH, and dosing regimen. RO did not appear to be linearly related to drug concentration. Results indicate that RO is an accurate predictor of in vivo pharmacodynamic activity and clinical efficacy.

One-year trial on safety and normal linear growth with flunisolide HFA in children with asthma.

Flunisolide hydrofluoroalkane (HFA) has efficacy equivalent to that of flunisolide chlorofluorocarbon (CFC) at one third the dose of the CFC formulation, a reduction from 250 microg/puff for flunisolide CFC to 85 microg/puff for flunisolide HFA. Flunisolide HFA delivers a smaller particle size (1.2 microm) in solution, resulting in improved lung deposition as compared with flunisolide CFC (3.8 microm), which is delivered in suspension. An added built-in spacer has reduced oropharyngeal deposition that may result in fewer adverse events and make it easier to use. The objective of this study was to compare the year-long safety of flunisolide HFA (daily dosage 340 microg) with that of CFC beclomethasone dipropionate (BDP) (daily dosage 336 microg) and cromolyn sodium (daily dosage 6,400 microg) in children 4-11 years old with mild-to-moderate asthma. The effects of these drugs on linear growth and growth velocity were also compared. The study was a 1-year open-label, parallel-group trial. Changes in physical examinations (including growth), adverse events, vital signs, electrocardiograms, cosyntropin stimulation tests, mouth and throat cultures for Candida albicans, and laboratory findings were analyzed. Patients 4-5 years old received flunisolide HFA only. In total, 235 children were evaluated (152 receiving flunisolide HFA, 39 BDP, and 44 cromolyn). The incidence of adverse events was comparable among treatment groups; most were mild or moderate and considered unrelated to treatment. Among patients 6-11 years old, mean changes from baseline height at week 52 were 6.2 cm for the flunisolide HFA and cromolyn groups and 5.1 cm for the BDP group. Thus growth in children receiving flunisolide HFA was unaffected by 1 year of treatment. Changes from baseline in other parameters, including response to cosyntropin stimulation, were insignificant and similar among the 3 treatment groups. At the dosages studied, and following 1 year of treatment, flunisolide HFA with its small particle size and built-in spacer is safe and well tolerated in children 4-11 years old. There are no adverse effects associated with hypothalamic pituitary axis (HPA) function of flunisolide HFA, including linear growth in children 6-11 years old when compared with BDP and cromolyn sodium.

The health-related quality of life effects of once-daily cetirizine HCl syrup in children with seasonal allergic rhinitis.

Seasonal allergic rhinitis (SAR) can adversely impact children's physical, psychological, and social functioning and well-being, that is, their health-related quality of life (HRQL). This study assessed HRQL in children 6 to 11 years treated with cetirizine HCl syrup, while concurrently assessing symptomatic relief and safety. In an open-label, non-comparative study, 544 children from 124 centers in the United States were instructed to take cetirizine HCl syrup (10 cc of 1 mg/mL) each evening for 4 weeks. Children experienced statistically significant improvements in HRQL with significant reductions in mean symptom score (p < 0.001) during the treatment period. Results were consistent across age groups (6-7, 8-9, 10-11 years). These results suggest that the symptomatic relief and tolerability profile of cetirizine HC1 syrup daily translates into improvements in the HRQL of children with SAR. This 4-week open label study is among the first to evaluate the effect of antihistamine treatment on HRQL outcomes in children.

Efficacy of fexofenadine versus desloratadine in suppressing histamine-induced wheal and flare.

To date, no published articles exist comparing the H1-receptor antagonist activities of fexofenadine and desloratadine using the histamine-induced skin wheal-and-flare model. The aim of this study was to compare the efficacy of fexofenadine versus desloratadine in suppressing histamine-induced skin flares and wheals in adults and adolescents. This was a two-center, randomized, placebo-controlled, complete-crossover study. Subjects were administered either single-dose fexofenadine HCl, 180 mg; desloratadine, 5 mg; or placebo and their response to skin-prick testing with histamine and diluent was recorded at predetermined time intervals. The primary end point was change in size of histamine-induced summation skin flares. Secondary end points included change in skin wheal summation measurements, onset, duration, maximum percent suppression, and time to maximum suppression of flares and wheals. Fexofenadine suppressed skin flares significantly more than desloratadine from 2 to 6 hours, and wheals from 2 to 4 hours, 6 to 9 hours, and 12 hours posttreatment. In addition, fexofenadine suppressed flares more than placebo at all time points from 2 to 24 hours and wheals more than placebo at all time points from 2 to 12 hours posttreatment. Desloratadine suppressed flares significantly more than placebo from 6 to 10 hours and at 12 and 24 hours but suppressed wheals significantly versus placebo only at 10 hours. Fexofenadine had a faster onset of flare suppression than desloratadine (1 hour versus 5 hours) and an equally rapid onset of wheal suppression. Fexofenadine HCl, 180 mg, was superior to desloratadine, 5 mg, in histamine-induced wheal-and-flare suppression, suggesting increased in vivo H1-receptor antagonist potency of fexofenadine versus desloratadine.