loratadine, Claritin
Inhibition of cytokine generation and mediator release by human basophils treated with desloratadine.

Schroeder JT, Schleimer RP, Lichtenstein LM, Kreutner W.

The Johns Hopkins Asthma and Allergy Center, Department of Medicine, Division of Clinical Immunology, Johns Hopkins University School of, Medicine, Baltimore, Maryland 21224, USA. schray mail.jhmi.edu

BACKGROUND: Desloratadine is a non-sedating, clinically effective, anti-allergic therapy that has been shown to exhibit anti-inflammatory properties that extend beyond its ability to antagonize histamine at H(1)-receptor sites. This latter effect has been shown in vitro to be both IgE-dependent and -independent. OBJECTIVE: In this study, we addressed the ability of desloratadine to inhibit the in vitro generation of interleukin (IL)-4 and IL-13 from human basophils while concurrently comparing its efficacy in preventing mediator release by these cells. METHODS: Basophil-enriched suspensions were treated with various concentrations of desloratadine for 15 min before stimulating with either anti-IgE antibody, calcium ionophore, IL-3 or phorbol ester. Histamine (fluorimetry), LTC(4) (RIA) and IL-4 (ELISA) were all assayed using the same 4-h culture supernatants. IL-13 (ELISA) was measured in supernatants harvested after 20 h incubation. IL-4 mRNA expression (dilutional RT-PCR) was also examined. RESULTS: Desloratadine was found to be nearly six-seven times more potent in preventing the secretion of IL-4 and IL-13 induced by anti-IgE than it was at inhibiting the release of histamine and LTC(4). These cytokines were equally inhibited by desloratadine following activation with ionomycin despite the lack of an effect on the histamine induced with ionomycin. Desloratadine had a lesser effect regarding inhibition of the IL-13 secreted in response to IL-3 and PMA. There was no evidence that desloratadine mediated its inhibitory effects by causing decreased cell viability. Finally, IL-4 mRNA accumulation was remarkably inhibited, by as much as 80%, following pretreatment with desloratadine. CONCLUSION: While capable of inhibiting histamine and LTC(4) release by human basophils, desloratadine is more effective at targeting the signals regulating IL-4 and IL-13 generation in these cells. This inhibitory effect on cytokine generation provides additional evidence that this antihistamine exerts anti-inflammatory properties.

Online source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=11591186&dopt=Abstract loratadine, Claritin



loratadine, Claritin
[Evaluation of loretadine therapy by rhino-manometry in patients with allergic rhinitis]

[Article in Hungarian]

Kosa L.

Svabhegyi Gyermekgyogyintezet, Gyermek Allergologiai Kozpont, Budapest.

The authors evaluated the nasal flow and resistance by rhinomanometry in 21 children suffering from ragweed allergy during the season. After this process the loratadine was administered for 1 month. During the therapy the nasal parameters were checked at 2 and 4 weeks, again. The loratadine significantly decreased the nasal resistance in 18 children and improved the nasal airflow in 17 cases. In the second part of the examination 15 ragweed sensitized children were undergone nasal allergen-specific challenge after 40 minutes taken loratadine. The nasal parameters were checked after 30 minutes and 6-8 hours. The statistical analyzes proved that loratadine can prevent and inhibit the early and late-phase of Type I hypersensitivity in contrast of the 12 children who were challenged without loratadine administration. They showed nasal obstruction. Based on the results, loratadine can be considered very effective antihistamine-antiallergenic drug which improves the quality of life of the allergic patients.

Online source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=10323075&dopt=Abstract loratadine, Claritin



loratadine, Claritin
The costs of nonsedating antihistamine therapy for allergic rhinitis in managed care: an updated analysis.

Liao E, Leahy M, Cummins G.

PharMetrics, Inc, 150 Coolidge Avenue, Watertown, MA 02471, USA.

OBJECTIVE: To update a prior study evaluating the use and costs of new-generation antihistamines for the treatment of allergic rhinitis in a managed care population. STUDY DESIGN: A retrospective database review of rhinitis-related medical and pharmacy-related claims during a treatment period of 12 months. METHODS: Patients who had been diagnosed as having allergic rhinitis and had at least 1 prescription claim were identified from a database containing patient-level medical and pharmaceutical claims. The treatment patterns for patients meeting study criteria were documented for a 12-month period to describe how nonsedating antihistamines are being used in allergic rhinitis, and to assess the associated costs of various medications. Subanalyses of patients categorized by comorbidity status were also performed. RESULTS: A total of 105,696 patients were included in this updated analysis, covering calendar year 1999. Nonsedating antihistamines were used by 68% of the sample, with loratadine and fexofenadine being the most commonly prescribed agents. The mean annual rhinitis-specific charge for fexofenadine-treated patients was $409 (standard deviation [SD] 727), which was significantly lower compared with charges for loratadine-treated patients, $424 (SD 740), P = .0144, or cetirizine-treated patients, $444 (SD 625), P < .0001. This trend was also observed in comparisons of patient subgroups. CONCLUSIONS: Consistent with our prior study, loratadine and cetirizine were generally associated with significantly higher treatment charges than fexofenadine. This result was observed across different stratifications of patients, including those with comorbid respiratory illness, concomitant use of nasal steroids, and asthma and/or sinusitis. These results provide further useful insights into the differential costs associated with the use of nonsedating antihistamines for allergic rhinitis treatment.

Online source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=11680261&dopt=Abstract loratadine, Claritin



loratadine, Claritin
[Effect of loratadine in children with allergic rhinitis]

[Article in Hungarian]

Kosa L, Kovacs N, Halasz A, Zsigmond G.

Legzesfunkcios Osztaly, Svabhegyi Allami Gyermekgyogyintezet, Budapest.

The authors examined 25 children with allergic rhinitis, who were sensitive to grass, weed and tree pollens. During the allergic season nasal lavage was performed then repeated after 4 weeks of loratadine treatment. Tryptase, IL-5, ECP, TNF-alpha and RANTES levels were measured from the nasal lavage fluid. Tryptase, IL-5, and ECP levels were decreased significantly while the decrease of RANTES and TNF-alpha levels was not significant. The authors emphasize that loratadine is an effective anti-inflammatory drug which affects the early and late phase of immediate hypersensitivity. In the moderate cases loratadine is enough to relieve the symptoms, while in the severe forms anti-allergic eye drops and nasal antihistamine or steroid spray has to be added.

Online source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=11681230&dopt=Abstract loratadine, Claritin



loratadine, Claritin
Inhibition of depolarization-induced [3H]noradrenaline release from SH-SY5Y human neuroblastoma cells by some second-generation H(1) receptor antagonists through blockade of store-operated Ca(2+) channels (SOCs).

Taglialatela M, Secondo A, Fresi A, Rosati B, Pannaccione A, Castaldo P, Giorgio G, Wanke E, Annunziato L.

Unit of Pharmacology, Department of Neuroscience, University of Naples Federico II, School of Medicine, Via S. Pansini 5, I-80131, Naples, Italy. mtaglial unina.it

In the present study, the effect of the blockade of membrane calcium channels activated by intracellular Ca(2+) store depletion on basal and depolarization-induced [3H]norepinephrine ([3H]NE) release from SH-SY5Y human neuroblastoma cells was examined. The second-generation H(1) receptor blockers astemizole, terfenadine, and loratadine, as well as the first-generation compound hydroxyzine, inhibited [3H]NE release induced by high extracellular K(+) concentration ([K(+)](e)) depolarization in a concentration-dependent manner (the IC(50)s were 2.3, 1.7, 4.8, and 9.4 microM, respectively). In contrast, the more hydrophilic second-generation H(1) receptor blocker cetirizine was completely ineffective (0.1-30 microM). The inhibition of high [K(+)](e)-induced [3H]NE release by H(1) receptor blockers seems to be related to their ability to inhibit Ca(2+) channels activated by Ca(i)(2+) store depletion (SOCs). In fact, astemizole, terfenadine, loratadine, and hydroxyzine, but not cetirizine, displayed a dose-dependent inhibitory action on the increase in intracellular Ca(2+) concentrations ([Ca(2+)](i)) obtained with extracellular Ca(2+) reintroduction after Ca(i)(2+) store depletion with thapsigargin (1 microM), an inhibitor of the sarcoplasmic-endoplasmic reticulum calcium ATPase (SERCA) pump. The rank order of potency for SOC inhibition by these compounds closely correlated with their inhibitory properties on depolarization-induced [3H]NE release from SH-SY5Y human neuroblastoma cells. Nimodipine (1 microM) plus omega-conotoxin (100 nM) did not interfere with the present model for SOC activation. In addition, the inhibition of depolarization-induced [3H]NE release does not seem to be attributable to the blockade of the K(+) currents carried by the K(+) channels encoded by the human Ether-a-Gogo Related Gene (I(HERG)) by these antihistamines. In fact, whole-cell voltage-clamp experiments revealed that the IC(50) for astemizole-induced hERG blockade is about 300-fold lower than that for the inhibition of high K(+)-induced [3H]NE release. Furthermore, current-clamp experiments in SH-SY5Y cells showed that concentrations of astemizole (3 microM) which were effective in preventing depolarization-induced [3H]NE release were unable to interfere with the cell membrane potential under depolarizing conditions (100 mM [K(+)](e)), suggesting that hERG K(+) channels do not contribute to membrane potential control during exposure to elevated [K(+)](e). Collectively, the results of the present study suggest that, in SH-SY5Y human neuroblastoma cells, the inhibition of SOCs by some second-generation antihistamines can prevent depolarization-induced neurotransmitter release.

Online source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=11705456&dopt=Abstract loratadine, Claritin



loratadine, Claritin
Pharmacokinetics of Loratadine in Pediatric Subjects.

Lin CC, Radwanski E, Affrime M, Cayen M.

Department of Drug Metabolism and Pharmacokinetics and Department of Clinical Pharmacology, Schering-Plough Research Institute, Kenilworth, USA.

The pharmacokinetics of loratadine, a new nonsedating antihistamine, was studied in 14 pediatric volunteers between the ages of 8 to 12 years. In an open-label design, one volunteer (with body weight less than 30 kg) received 5 mg of loratadine syrup and 13 volunteers (with body weights greater than 30 kg) received 10 mg of loratadine syrup. Blood samples were collected up to 72 h after dosing. Plasma concentrations of loratadine and its metabolite, descarboethoxyloratadine, were determined by a specific and sensitive gas-liquid chromatographic method. Following a 10-mg dose as a syrup, plasma concentrations of loratadine and descarboethoxyloratadine could be determined up to 8 and 48 h, respectively. The maximum concentration (C(max)) of loratadine and descarboethoxyloratadine were approximately 4 ng ml(minus sign1) each. However, the AUC of the metabolite was about six times that of loratadine. The elimination phase half-life of descarboethoxyloratadine averaged about 13.8 hr. The pharmacokinetics of loratadine in pediatric subjects was similar to that in healthy adult volunteers.

Online source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=11850699&dopt=Abstract loratadine, Claritin