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Medical research on allegra
Int J Pharm. 2008 May 14;
Ujie K, Oda M, Kobayashi M, Saitoh H
It has been shown that fexofenadine, a selective non-sedating histamine H(1)-receptor antagonist, is a substrate for P-glycoprotein (P-gp) and an organic anion transporting peptide (OATP). This study was undertaken to investigate the relative contribution of these absorptive and secretory transporters to the intestinal absorption of fexofenadine in rats. When 0.1mM fexofenadine was introduced into duodenal, jejunal, and ileal loops, its disappearance was around 10% over 30min. Cyclosporine A, but not ketoconazole, probenecid or mitoxantron, significantly increased fexofenadine disappearance in the ileal loops. The serosal-to-mucosal permeation of fexofenadine across the rat ileal segments was approximately 18-fold greater than its mucosal-to-serosal permeation. The secretory orientation of the ileal permeation of fexofenadine was weakened significantly in the presence of cyclosporine A, moderately in the presence of ketoconazole, but was unchanged in the presence of probenecid. When fexofenadine (0.1 or 0.5mM) was administered to rats intraluminally, plasma concentrations increased linearly up to 120min. The magnitude of the increase in plasma fexofenadine concentrations in the presence of cyclosporine A was more remarkable at 0.5mM than at 0.1mM. The results obtained in this study suggest that the intestinal absorption of fexofenadine is relatively small in rats even if OATP functions as an absorptive transporter for fexofenadine. Low absorption of fexofenadine in rats is attributed to potent secretory transport mediated by P-gp.
Expert Opin Pharmacother. 2008 Jul; 9(10): 1655-65
Lee HW, Lee HW, Park DJ, Moon SO, Ahn JH, Kim MJ, Kim SD, Kim JE, Yoon YR
OBJECTIVES: To compare the effects of a first-generation antihistamine, chlorpheniramine, with those of the second-generation antihistamine, fexofenadine, at steady-state, on nocturnal sleep architecture in healthy Korean volunteers using polysomnography and the Multiple Sleep Latency Test. We evaluated whether a genetic polymorphism of multi-drug resistance 1 gene (MDR1) could produce variations in pharmacokinetic and pharmacodynamic parameters of fexofenadine. DESIGN/METHODS: Ten healthy male volunteers received one capsule of fexofenadine 180 mg once each morning or chlorpheniramine 6 mg (2 mg in the morning and 4 mg after 12 h) for 3 days, in a single-site, randomized, double-blind, two-treatment, multiple-dosing, two-way crossover study, with a washout period of 7 days. Overnight polysomnography was measured on the second night of the treatment period. The Multiple Sleep Latency Test was carried out the next morning. Blood samples were taken for the assessment of fexofenadine pharmacokinetics and MDR1 genotyping on the third day. RESULTS: Compared with baseline and fexofenadine, chlorpheniramine significantly increased the latency in rapid eye movement (REM) sleep, with no significant decrease in the percentage of REM sleep. No significant change in latency for REM sleep or percentage REM sleep after dosing with fexofenadine was observed. There was no significant change in the daytime sleepiness with fexofenadine and chlorpheniramine. The effects of MDR1 genotypes and haplotypes on the pharmacokinetics and pharmacodynamics of fexofenadine were not significant. CONCLUSIONS: Our findings suggest that fexofenadine and chlorpheniramine at steady-state have no significant effect on nocturnal sleep variables and daytime sleepiness, when compared to baseline.
Diffusion Tensor Imaging Findings in First-Episode and Chronic Schizophrenia Patients.
Am J Psychiatry. 2008 Jun 16;
Friedman JI, Tang C, Carpenter D, Buchsbaum M, Schmeidler J, Flanagan L, Golembo S, Kanellopoulou I, Ng J, Hof PR, Harvey PD, Tsopelas ND, Stewart D, Davis KL
Objective Comparisons of diffusion tensor imaging (DTI) data between first-episode and chronic schizophrenia patients assessed in different studies have led to the suggestion that the decreased fractional anisotropy observed in chronic schizophrenia patients is less pronounced in first-episode patients. However, such comparisons of imaging data generated across studies are susceptible to numerous confounders, which may limit the interpretation of any differences. In order to address these issues and determine whether the DTI abnormalities of chronic schizophrenia are present at illness onset, the authors conducted a DTI investigation of the largest cohort of first-episode schizophrenia patients yet reported in conjunction with a group of chronic schizophrenia patients and healthy subjects for comparison. Method Fractional anisotropy data generated by diffusion tensor imaging with a 3-T Siemens Allegra head-dedicated MRI system were compared between 40 first-episode schizophrenia patients and 39 age- and gender-matched healthy comparison subjects and between 40 chronic schizophrenia patients and 40 age- and gender-matched healthy comparison subjects. The following regions of interest were assessed: forceps minor (bilaterally), forceps major (bilaterally), inferior longitudinal fasciculus (bilaterally), and the genu and splenium of the corpus callosum. Results In most regions, chronic schizophrenia patients showed significant or trend-level lower fractional anisotropy than healthy comparison subjects, whereas the first-episode schizophrenia patients showed only trend-level lower fractional anisotropy in the inferior longitudinal fasciculus. Conclusions The cross-sectional data reported here suggest less widespread changes in white matter at illness onset in schizophrenia which progress in more chronic states. More definitive conclusions will require follow-up imaging of first-episode schizophrenia patients.
Ann Allergy Asthma Immunol. 2008 May; 100(5): 452-6
Jones DH, Romero FA, Casale TB
BACKGROUND: Diphenhydramine is often the treatment of choice for acute urticarial or allergic reactions despite its adverse effects of sedation and impairment. Second- and third-generation histamine1-antihistamines are generally devoid of these adverse effects but are typically not used because of a perceived slower onset of action. OBJECTIVE: To examine the time-dependent effects of oral fexofenadine and oral and intramuscular diphenhydramine to reduce histamine-induced wheal-and-flare responses. METHODS: Eighteen healthy patients were included in a double-blind, placebo-controlled, 3-way, randomized, crossover study with oral fexofenadine (180 mg) and oral and intramuscular diphenhydramine (50 mg). Histamine-induced skin tests were performed before and more than 6 hours subsequent to dosing. The primary end point was time to induce a 50% reduction in histamine-induced flare. Secondary end points included change from baseline at each time point in wheal-and-flare responses and area under the curve at more than 6 hours for flare. RESULTS: No significant differences were found in the 50% inhibitory responses of histamine-induced flares among the 3 groups (P = .09). No significant differences were found among the 3 groups in change from baseline at each time point except for 30 minutes during which fexofenadine had no inhibitory effect. Area under the curve analyses for wheal-and-flare responses revealed no differences among treatments at more than 6 hours. CONCLUSION: Diphenhydramine tended to work more rapidly than fexofenadine, but the differences were not statistically significant. Given the adverse effect profile of diphenhydramine, but only marginal onset of action advantage, the risk-to-benefit ratio may be more favorable for oral fexofenadine when treating an acute urticarial or allergic reaction.
Arthroscopy. 2008 Jun; 24(6): 689-96
Checcucci G, Allegra A, Bigazzi P, Gianesello L, Ceruso M, Gritti G
PURPOSE: We propose a new technique of regional anesthesia that combines suprascapular nerve block (SSNB) and axillary nerve block (ANB) in arthroscopic shoulder surgery. METHODS: Twenty consecutive patients undergoing arthroscopic procedures for shoulder cuff diseases were included in the trial. SSNB was performed by introducing the stimulating needle approximately 2 cm medial to the medial border of the acromion and about 2 cm cranial to the superior margin of the scapular spine until supraspinatus or infraspinatus muscle contractions were elicited. Following negative aspiration, 15 mL of a mixture of 2% lidocaine (5 mL) and 0.5% levobupivacaine (10 mL) was injected. ANB was performed; a line was drawn between the lateral-posterior angle of the acromion and the olecranon tip of the elbow. The location was about 2 cm cranial to the convergence of this line with the perpendicular line from the axillary fold. The needle was introduced approximately 2 cm cranial to this crossing point to elicit deltoid muscle contractions, and another 15 mL of the same anesthetic mixture was injected. Five mL of the same mixture was injected into each portal of the arthroscopic area. During surgery, patients were sedated with the use of midazolam. General anesthesia was not performed. Acceptance of the technique was assessed through a postsurgical survey of those treated. RESULTS: No serious complications occurred. None of the patients required opiates, analgesics, or general anesthesia during the surgical procedure. Postoperative pain control, which was assessed using a visual analog scale, was effective during the observation time. The total demand for nonopiate analgesics during the first 24 postoperative hours was negligible. Patient satisfaction and comfort were satisfactory. CONCLUSIONS: Combining SSNB and ANB is an effective and safe technique for intraoperative anesthesia and postoperative analgesia for certain procedures of shoulder arthroscopic surgery.
Probenecid, but Not Cystic Fibrosis, Alters the Total and Renal Clearance of Fexofenadine.
J Clin Pharmacol. 2008 May 29;
Liu S, Beringer PM, Hidayat L, Rao AP, Louie S, Burckart GJ, Shapiro B
This study aims to evaluate renal P-glycoprotein (P-gp) activity in patients with cystic fibrosis. P-gp efflux activity in peripheral T cells was measured by flow cytometry in 10 cystic fibrosis and 15 healthy volunteers. Eight cystic fibrosis patients and 8 healthy volunteers were recruited into a crossover pharmacokinetic study in which participants received 180 mg fexofenadine with or without 1 g probenecid twice a day. Genotyping was performed for ABCB1 C1236T, G2677T, and C3435T. P-gp efflux activity in peripheral T cells was not significantly different between cystic fibrosis patients and healthy volunteers. No difference in fexofenadine pharmacokinetic parameters was observed between cystic fibrosis patients and healthy volunteers when fexofenadine was administered with or without probenecid. Coadministration of probenecid significantly increased fexofenadine AUC and decreased the cumulative urinary excretion, total body clearance, and renal clearance. ABCB1 3435 C/T carriers showed increased basal P-gp activity in CD4+ and CD8+ T cells, increased R123-induced efflux activity in CD4+ T cell, and decreased fexofenadine AUC. Fexofenadine disposition and P-gp efflux activity in peripheral T cells was similar between cystic fibrosis patients and healthy volunteers. Probenecid administration significantly reduced the total body and renal clearance of fexofenadine. ABCB1 3435 C/T was associated with an elevated efflux activity compared with C/C subjects.
Don Quixote and the quest for personalized medicine.
J Clin Oncol. 2008 Jun 1; 26(16): 2619-20
Allegra CJ, Benedetti JK
Environ Sci Technol. 2008 Apr 1; 42(7): 2708-9; author reply 2710
Cetta F, Dhamo A, Schiraldi G, Allegra L
Hematol Oncol. 2008 May 27;
Alonci A, Allegra A, Bellomo G, Penna G, D'Angelo A, Quartarone E, Musolino C
Authors evaluated some markers of angiogenetic activity in patients with chronic myeloproliferative diseases (CMDs). In this study by using a cytofluorimetric analysis we evaluated circulating endothelial progenitor cells (EPCs) in patients with chronic myeloproliferative disease. Moreover, in the same group of subjects, we evaluated serum levels of vascular endothelial growth factor (VEGF) and vascular endothelial growth factor receptor-2 (VEGFR2). In our patients, we have found an increase in the number of endothelial progenitor cells in primary myelofibrosis (PMF) and polycythaemia vera (PV) patients, while an increase of circulating endothelial cells (CECs) was found in all patients with CMD. Moreover, we found higher serum levels of VEGF with respect to control subjects in every group of patients with CMD, and a not significant reduction of VEGFR2 levels in essential thrombocythaemia (ET) patients. A correlation was also found in PV patients between VEGF levels and erythrocyte number and in PMF subjects with the count of white cells. Our data suggest that some markers of angiogenesis are activated in CMD patients and angiogenesis may have a role in the pathophysiology of chronic myeloproliferative disorders. Copyright (c) 2008 John Wiley & Sons, Ltd.
Propionyl-l-Carnitine in Leriche-Fontaine Stage II Peripheral Arterial Obstructive Disease.
Ann Vasc Surg. 2008 May 23;
Allegra C, Antignani PL, Schachter I, Koverech A, Messano M, Virmani A
Peripheral arterial obstructive disease (PAOD) of the lower limbs affects 5% of the adult population. Uncontrolled arteriopathy is established due to a microcirculatory deficit, which may be present despite a good Winsor index and which leads to exhaustion of the functional microcirculatory reserve. The target of this study was to examine possible improvements in microvascular and tissue homeostasis by the administration of propionyl-L-carnitine (PLC). A total of 26 patients were enrolled in this study, aged 65 +/- 15 years; two males were diagnosed at stage IIA and 17 males and seven females at stage IIB PAOD. The main criterion of inclusion was the worsening of walking distance during the last month. In this study the duration of therapy was 33 days. PLC was administered in three flasks, each containing 300 mg in 250 cc saline by continuous infusion. The following parameters were measured before and after treatment: pain-free and maximum walking distance (measured on a treadmill at 3.2 km/hr with a gradient of 12%), recovery time from pain after maximum walking distance, ankle-brachial index by means of the Doppler apparatus, and evaluation of the microcirculation using capillaroscopy. The results showed that therapy with PLC was effective at restoring activity of skeletal muscle in ischemic conditions. In particular, capillaroscopy showed improvement in the angioarchitecture in the microcirculation fields, expressed as increased numbers of visible capillaries and diminution in the time of loss of sodium fluorescein marker. The clinical data showed increased walking distance and diminished time to recover from pain, and the clinical improvement correlated with improved microcirculatory function. From these preliminary data has emerged an indication of therapy with PLC for chronic obstructive arteriopathy of the lower limbs at stage II. Further studies with higher numbers of patients and more controlled variables are planned.