Our library of drug research abstracts drawn from the medical literature is updated on a regular schedule, and you can be assured that new atarax research articles will be listed here shortly after becoming available to us.
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Medical research on atarax
Curr Med Chem. 2008; 15(21): 2173-91
Chen C
Cetirizine, marketed as a racemic mixture containing both levocetirizine and dextrocetirizine, is a member of the second generation H(1) antihistamines clinically used for the treatment of symptoms associated with seasonal allergic rhinitis. Recently, its single R-enantiomer levocetirizine has been approved by the FDA as the newest antihistamine. Cetirizine is a piperazine derivative related to the first generation H(1) antagonist hydroxyzine, and is the major metabolite in the blood circulation after hydroxyzine administration in humans. The acid functionality of cetirizine in combination with one of the basic nitrogens of piperazine ring makes this compound a very unique zwitterion. The molecular structure of cetirizine allows its carboxylic group to interact with the basic nitrogen via folded conformers, therefore, it possesses relatively high lipophilicity at physiological pH (LogD=1.5). While both cetirizine and hydroxyzine possess high affinity at the H(1) receptor, the R-configured levocetirizine has much slower dissociation rate from the H(1) receptor than R-hydroxyzine, making it an insurmountable antagonist. In addition, the pharmacokinetics of cetirizine significantly differs from those of the basic and lipophilic hydroxyzine. For example, cetirizine has much lower CNS penetration than hydroxyzine, which may be explained by the zwitterionic structure of cetirizine and its P-glycoprotein activity. Cetirizine exhibits high intestinal absorption in humans and its oral bioavailability is estimated to be greater than 70%. Very importantly, cetirizine, especially levocetirizine, has a negligible interaction with the liver enzymes, and is mainly excreted in the urine as the parent despite its high plasma protein binding (88 approximately 96%). The recommended dose of levocetirizine is 5 mg once daily, while its pharmacokinetic half-life is about 7 h in humans. This review will focus on the physicochemical, pharmacological and pharmacokinetic properties of cetirizine and levocetirizine in comparison with those of hydroxyzine. The zwitterionic cetirizine displays distinct advantages over the basic hydroxyzine in several categories such as slow receptor dissociation rate, high selectivity, negligible liver enzyme interaction and low CNS penetration. Therefore, cetirizine, or its single isomer levocetirizine, might serve a good example for medicinal chemists to design zwitterionic drugs from a basic, acidic or neutral lead molecule for peripheral biological targets.
Treatment of chronic autoimmune urticaria with omalizumab.
J Allergy Clin Immunol. 2008 Sep; 122(3): 569-73
Kaplan AP, Joseph K, Maykut RJ, Geba GP, Zeldin RK
BACKGROUND: Approximately 45% of patients with chronic urticaria have an IgG autoantibody directed to the alpha-subunit of the high-affinity IgE receptor (chronic autoimmune urticaria, CAU) leading to cutaneous mast cell and basophil activation. Treatment of allergic asthma with omalizumab produces rapid reduction in free IgE levels and subsequent decrease in Fc epsilon RI expression on mast cells and basophils. If this occurs in CAU, cross-linking of IgE receptors by autoantibody would be less likely, reducing cell activation and urticaria/angioedema. OBJECTIVE: To investigate the efficacy of omalizumab in patients with CAU symptomatic despite antihistamine therapy. METHODS: Twelve patients with CAU, identified by basophil histamine release assay and autologous skin test, with persistent symptoms for at least 6 weeks despite antihistamines, were treated with placebo for 4 weeks followed by omalizumab (>or=0.016 mg/kg/IU mL(-1) IgE per month) every 2 or 4 weeks for 16 weeks. Primary efficacy variable was change from baseline to the final 4 weeks of omalizumab treatment in mean Urticaria Activity Score (UAS, 0-9 scale). Changes in rescue medication use and quality of life were assessed. RESULTS: Mean UAS declined significantly from baseline to the final 4 weeks of omalizumab treatment (7.50 +/- 1.78 to 2.66 +/- 3.31, -4.84 +/- 2.86, P = .0002). Seven patients achieved complete symptom resolution. In 4 patients, mean UAS decreased, but urticaria persisted. One patient did not respond. Rescue medication use was reduced significantly, and quality of life improved. No adverse effects were reported or observed. CONCLUSION: This exploratory proof of concept study suggests omalizumab is an effective therapy for CAU resistant to antihistamines.
Fexofenadine effects on cognitive performance in aviators at ground level and simulated altitude.
Aviat Space Environ Med. 2008 Aug; 79(8): 754-60
Vacchiano C, Moore J, Rice GM, Crawley G
INTRODUCTION: Antihistamines are used for the treatment of allergic rhinitis (AR) symptoms. However, the cognitive effects of some antihistamines can dramatically impair individuals in occupations that require sustained vigilance. METHODS: The cognitive effects of fexofenadine were compared to a placebo (passive control) and cetirizine (active control) in healthy naval flight personnel. All subjects received one dose of each treatment in one of six possible sequences with two washout periods in between, and were assessed for aviation-related cognitive skills using the Aeromedical Vigilance Test (AVT) at both ambient atmospheric conditions and normobaric hypoxic conditions. Drowsiness was self-assessed by participants using a visual analog scale (VAS). RESULTS: There was no significant difference between fexofenadine and placebo over the entire 60-min test period, under ambient atmospheric conditions, or under either hypoxic condition. Compared with placebo, cetirizine significantly increased AVT errors over the entire 60-min test period, at 10,000 ft, and at 15,000 ft. No statistical difference was found between treatments under ambient atmospheric conditions, although cetirizine treatment resulted in a greater change from baseline in adjusted average number of AVT errors (0.2124 +/- 0.06) than fexofenadine treatment (0.1989 +/- 0.07) and placebo (0.0745 +/- 0.07). Furthermore, at 10,000 ft there were significantly more AVT errors with cetirizine than with fexofenadine. There were no significant increases in self-reported drowsiness (VAS) for both cetirizine and fexofenadine compared with placebo. CONCLUSION: Fexofenadine is comparable to placebo in its effect on the cognitive skills important for piloting an aircraft, while cetirizine impairs cognition and may affect piloting ability.
[The use of atarax in the treatment of attention deficit syndrome with hyperactivity and anxiety]
Zh Nevrol Psikhiatr Im S S Korsakova. 2007; 107(7): 62-4
Chutko LS, Lapshina OV, Surushkina SIu
Clin Exp Dermatol. 2008 Aug 2;
Tosoni C, Lodi-Rizzini F, Cinquini M, Pasolini G, Venturini M, Sinico RA, Calzavara-Pinton P
Background. Urticarial vasculitis (UV) is an uncommon type of chronic urticaria (CU), which exhibits leucocytoclastic vasculitis. Painful and long-lasting (> 24 h) weals associated with purpura or bruising are considered indicative of UV. It is often responsive to oral corticosteroids and poorly to oral antihistamines. Hypocomplementaemia and systemic involvement are also commonly reported. Aims. To diagnose patients with UV histologically and then compare their clinical features and response to various treatment regimens. Methods. Biopsies were taken from 312 subjects with CU unresponsive to oral antihistamines; of these, 47 were histologically diagnosed as having UV. Biopsies were taken irrespective of the clinical features of weal eruption. Other diseases known to be associated with small-vessel vasculitis had previously been excluded. Results. Individual weals lasted < 24 h in 57.4% of patients, and pain or tenderness was reported only by 8.6%. Extracutaneous features were present in 81%, hypocomplementaemia in 11% and abnormalities of other laboratory parameters (i.e. raised erythrocyte sedimentation rate, microscopic haematuria) in 76.6%. Hydroxyzine was effective in only one patient. Both oral corticosteroids and cinnarizine were effective in a high percentage of the patients. Conclusion. This diagnostic approach allowed us to identify a large group (47 patients) with UV. Most did not present the clinical (prolonged duration of weals and bruising) and laboratory features that have previously been described as characteristic of UV. Cinnarizine was found to be a valuable treatment option.
Drugs Aging. 2008; 25(8): 683-92
Hosia-Randell HM, Muurinen SM, Pitkälä KH
BACKGROUND AND OBJECTIVE: Multiple drug use is common among old, frail nursing home residents who are, as a consequence, susceptible to adverse effects and drug interactions. This study uses the updated Beers criteria for potentially inappropriate drug (PID) use in older adults to determine the extent and nature of PIDs in older nursing home residents in Helsinki, Finland. The study also uses the Swedish, Finnish, INteraction X-referencing (SFINX) interaction database to assess the possibility of clinically significant class D ("clinically significant interaction, and the combination should be avoided") drug-drug interactions (DDIs) in the same population. METHODS: This study is a cross-sectional assessment of all nursing home residents aged > or = 65 years in Helsinki. The residents' demographic information and medical data were collected from medical charts in February 2003. RESULTS: Of all nursing home residents in Helsinki, 82% (n = 1987) were eligible for analysis. Their mean age was 83.7 (SD 7.7) years, 80.7% were female and 69.5% were diagnosed with dementia. The mean number of drugs given on a regular basis per resident was 7.9 (SD 3.6) per day. Of the study population, 34.9% regularly used at least one PID. Residents taking PIDs were more likely to be taking psychotropic medication and to be taking nine or more drugs daily, and less likely to have a diagnosis of dementia, than patients not taking PIDs. The three most prevalent PIDs were: (i) short-acting benzodiazepines in greater than recommended doses (13.9% of all residents), of which temazepam >15 mg/day was the most commonly used agent and, indeed, the most common PID (taken by 13.5% of all residents); (ii) hydroxyzine (7.1%); and (iii) nitrofurantoin (6.3%). Together, these three PIDs accounted for 76.9% of all PID use. Of all residents, 4.8% were susceptible to a clinically significant DDI. The most common potential DDIs were related to the use of potassium-sparing diuretics, carbamazepine and codeine. Compared with residents not exposed to potential DDIs, residents exposed to potential DDIs were more likely to be younger, to have a prior history of stroke, to be taking psychotropics, to be taking nine or more drugs daily and to be taking PIDs. CONCLUSION: Use of PIDs is very common among nursing home residents, and this increases the likelihood of DDIs. Monitoring patients for PID use and potential drug interactions could increase the quality of prescribing.
Oral montelukast and cetirizine for thyroid eye disease.
Ophthal Plast Reconstr Surg. 2008 Jul-Aug; 24(4): 257-61
Lauer SA, Silkiss RZ, McCormick SA
PURPOSE: To study the efficacy of oral montelukast, a cysteinyl leukotriene receptor antagonist, in combination with cetirizine, a histamine-1 receptor antagonist, in the treatment of thyroid eye disease. METHODS: Patients considering surgical correction of eyelid retraction for inflammatory symptoms of thyroid eye disease were offered a preoperative medical regimen of oral montelukast/cetirizine. Exclusion criteria included prior use of oral montelukast (i.e., for seasonal allergy or asthma), compressive optic neuropathy, severe ophthalmopathy requiring systemic corticosteroids, and orbital and/or muscle surgery. A 6-week course of oral cetirizine (10 mg every morning) and oral montelukast (10 mg every evening) was administered and patients subjectively rated their ocular surface dryness, tearing, itching, injection, eyelid swelling, eyelid retraction, double vision, proptosis, and visual clarity, at baseline, after 3 weeks and 6 weeks of medical therapy, and after 3 weeks off of the medications. RESULTS: Six of the 12 patients recruited for the study reported a subjective improvement in tearing, dryness, and itching. Less effect on diplopia and proptosis was noted after 6 weeks of medical therapy. Two of the patients who did not report response chose to proceed with eyelid retraction surgery and both had evidence of mast cell infiltration in their Müller muscle specimens. CONCLUSION: The response observed in this open-label trial suggests that oral montelukast and cetirizine may be an effective medical regimen for patients with thyroid eye disease who experience mild to moderate orbital congestion and inflammation.
Allergy. 2008 Jul; 63(7): 924-31
Fantin S, Maspero J, Bisbal C, Agache I, Donado E, Borja J, Mola O, Izquierdo I,
BACKGROUND: With the current increasing incidence of allergies worldwide, new treatments showing efficacy and long term safety are needed for chronic conditions such as persistent allergic rhinitis (PER). New generation H1-antihistamines have demonstrated anti-allergic properties, which could possibly enhance their effectiveness in long-term periods of treatment. OBJECTIVE: To investigate the efficacy of rupatadine, in controlling symptoms of PER over a 12-week period. METHODS: A randomized, double blind, parallel-group, placebo-controlled study was carried out in patients aged older than 12 years with PER. Main inclusion criteria were: instantaneous total symptom score (i6TSS) >or=45, nasal obstruction score or=2 as moderate during the first visit. The primary efficacy endpoint was the 12-week average change from baseline of the patients' i6TSS. RESULTS: In all, 736 patients were selected. Of them, 543 (73.8%) were randomized in three different groups: placebo (n = 185), cetirizine (n = 175) and rupatadine (n = 183). Rupatadine (P = 0.008) but not cetirizine (P = 0.07) statistically reduced the baseline i6TSS vs placebo (47.8%, 44.7% and 38.8%, respectively), after 12 weeks. Onset of action was observed at the first 24 h for both treatments (rupatadine vs placebo, P = 0.013; cetirizine vs placebo, P = 0.015). Furthermore, instantaneous total nasal symptoms score (iTNSS) (including nasal blockage) mean change from baseline showed a significant reduction with rupatadine 10 mg in comparison with placebo, along all treatment duration of 12 weeks. Study treatments were well tolerated. CONCLUSION: Rupatadine significantly relieves symptoms of PER, providing a rapid onset of action and maintains its effects over a long period of 12-weeks.
Am J Obstet Gynecol. 2008 Jul; 199(1): 71.e1-10
Stanford EJ, Chen A, Wan GJ, Lunacsek OE, Sand PK
OBJECTIVE: The aim of this study was to examine treatment modalities, health care resource utilization, and costs in patients diagnosed with interstitial cystitis (IC). STUDY DESIGN: Patients with a diagnosis of IC were identified from a national managed care administration claims database and classified into treatment cohorts. All-cause health care resource utilization and costs were calculated by treatment cohort. RESULTS: Patients treated with narcotics plus nonnarcotic analgesics were associated with higher mean health care costs. Patient cohorts treated with some of the more common oral therapies for interstitial cystitis, including pentosan polysulfate sodium, amitriptyline, and hydroxyzine, were associated with lower costs. Physician visits were fewest among patients treated with pentosan polysulfate sodium plus amitriptyline and hydroxyzine. Physician visits were higher for cohorts that included dimethyl sulfoxide plus cystoscopy or bladder irrigation, or narcotics plus nonnarcotic analgesics. CONCLUSION: Interstitial cystitis is associated with substantial costs and health care resource utilization.
[Does new antihistamines characterize tachyphylaxis phenomenon?]
Otolaryngol Pol. 2007; 61(5): 898-901
Kłos K, Kruszewski J
THE AIM OF THE STUDY: was to estimate the skin microcirculation reactivity after histamine administration in patients treated with 10 mg daily dose of cetirizine for 180 days. MATERIAL AND METHODS: Thirty seven young men age 27+12 year, patients suffering from persistent rhinitis were randomized into three groups which received 10 mg/day of cetirizine, 5 mg/day of levocetirizine or placebo respectively. Twenty eight completed the study. The skin microcirculation reaction after 10 mg/ml histamine administration was estimated visually on the forearm (diameter of wheal and flare) and by laser Doppler flowmetry before and after study drug or placebo administration 24 hours and every 30 days during the time of the study. The blood flow was measured by Periflux PF3, using a skin probe 5 mm away from the histamine-induced point. RESULTS: Statistically significant inhibition of skin reaction (over 92%) and blood flow (over 85%) in relation to the start values in cetirizine group as well as between the groups which received cetirizine or placebo (p