loratadine, Claritin
The effects of astemizole, cetirizine and loratadine on the time course of weal and flare reactions to histamine, codeine and antigen.

Humphreys F, Hunter JA.

University Department of Dermatology, Royal Infirmary, Edinburgh, U.K.

An open cross-over study was performed to assess the effects of astemizole, cetirizine and loratadine on weal and flare reactions to intradermal histamine, codeine and house dust mite antigen. Percentage inhibition of weal area, flare area and weal volume was greatest for cetirizine, then astemizole and smallest for loratadine. Wealing due to mast-cell degranulation with either codeine or antigen was less inhibited by all three antihistamines than that due to histamine itself. Time-course studies revealed similarities between wealing provoked by codeine and histamine but different characteristics to that induced by antigen.

Online source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=1683252&dopt=Abstract loratadine, Claritin



loratadine, Claritin
Selective inhibition of peripheral histamine responses by loratadine and terfenadine.

Mauser PJ, Kreutner W, Egan RW, Chapman RW.

Department of Allergy and Immunology, Schering-Plough Research, Bloomfield, NJ 07003.

To determine the selectivity of the non-sedating antihistamines loratadine and terfenadine and the sedating antihistamine diphenhydramine for peripheral and central histamine H1-receptors, these compounds were examined against intravenous (i.v.) and intracerebroventricular (i.c.v.) histamine-induced bronchoconstriction in anesthetized, spontaneously breathing guinea pigs. Animals were prepared with i.c.v. or i.v. cannulas and instrumented for the measurement of airway resistance (RAW) and dynamic lung compliance (CDyN). Loratadine, terfenadine or diphenhydramine were administered orally 2 h before either i.v. or i.c.v. injection of histamine. Each antihistamine blocked the i.v. histamine bronchospasm with the order of potency loratadine (ED40 = 0.08 mg/kg) greater than terfenadine (ED40 = 0.44 mg/kg) greater than diphenhydramine (ED40 = 5 mg/kg). These drugs also blocked i.c.v. histamine-induced bronchoconstrictions, but loratadine and terfenadine were approximately 10 times less potent against i.c.v. histamine bronchoconstriction than they were against i.v. histamine. In contrast, diphenhydramine was equipotent against i.c.v. and i.v. histamine bronchoconstriction. These results demonstrate that the non-sedating antihistamines loratadine and terfenadine, unlike diphenhydramine, are more effective against peripheral than central H1-receptors, probably because of poor penetration of the blood-brain barrier.

Online source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=1698159&dopt=Abstract loratadine, Claritin



loratadine, Claritin
Pharmacology of antihistamines.

Woodward JK.

Merrell Dow Research Institute, Merrell Dow Pharmaceuticals Inc., Cincinnati, OH 45215.

Unlike the classic antihistamines, the new H1-receptor antagonists do not block cholinergic or central H1 receptors and thus do not produce the side effects, such as sedation, impaired psychomotor performance, and excessive mucosal drying, that are commonly associated with the older agents. Important pharmacokinetic and pharmacodynamic differences that exist among this class of antihistamines translate into varying pharmacologic effectiveness. Terfenadine, loratadine, and cetirizine are all rapidly absorbed in healthy and allergic volunteers (peak plasma levels, 2 to 5 hours); astemizole, however, has an initial distribution phase of 2 to 3 days. Further, astemizole has the longest time to relief of symptoms in this class; histamine wheal inhibition is not apparent until the second day of 10 mg dosing and does not peak for 9 to 12 days. In comparison, terfenadine's antihistaminic action peaks at 3 to 4 hours, loratadine's at 4 to 6 hours, and cetirizine's at 4 to 10 hours. However, whereas the recommended dose of loratadine (10 mg) confers 50% wheal inhibition, 60 mg terfenadine produces an 85% to 90% inhibition. In addition, loratadine and cetrizine have apparent dose-related sedative effects.

Online source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=1977782&dopt=Abstract loratadine, Claritin



loratadine, Claritin
Pharmacokinetics of loratadine in patients with renal insufficiency.

Matzke GR, Halstenson CE, Opsahl JA, Hilbert J, Perentesis G, Radwanski E, Zampaglione N.

Department of Medicine, Hennepin County Medical Center, Minneapolis, MN 55415.

The disposition of loratadine, a new orally active histamine H1 receptor antagonist and its primary metabolite descarboethoxyloratadine were characterized in adult volunteers with normal renal function (group I), patients with chronic renal failure, i.e., creatinine clearance less than 30 mL/min (group II), as well as chronic hemodialysis patients (group III). The effect of hemodialysis on the disposition of loratadine and descarboethoxyloratadine was also assessed. Subjects in groups I and II were given a single oral 40 mg dose of loratadine while the patients in Group III received two single 40 mg doses of loratadine (during an interdialytic period and just prior to hemodialysis). Loratadine was rapidly absorbed and the decline of plasma concentrations after attainment of the Cmax was biexponential in all subjects. No significant differences in t1/2 beta were observed between the three groups (8.7 +/- 5.9, 7.6 +/- 6.9, 8.6 +/- 1.6 hrs: in groups I, II, and III, respectively). The apparent total body clearance and apparent volume of distribution of loratadine also did not differ significantly among the three groups. No significant differences in the Cmax or tmax of the metabolite were observed. The metabolite AUC infinity 0 however was significantly greater in group II subjects: (212.4 +/- 37.8, 469.5 +/- 95.4, 325.2 +/- 114.6 ng.hr/mL; groups I, II, and III, respectively). No significant relationship was observed between the terminal elimination half-life of loratadine or descarboethoxyloratadine and creatinine clearance. Hemodialysis augmented endogenous clearance by less than 1%. The disposition of loratadine is not significantly altered in patients with severe renal insufficiency nor is hemodialysis an effective means of removing loratadine or descarboethoxyloratadine from the body.

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loratadine, Claritin
Antiallergic activity of loratadine, a non-sedating antihistamine.

Kreutner W, Chapman RW, Gulbenkian A, Siegel MI.

Loratadine is a new non-sedating antihistamine. The present studies compared loratadine and terfenadine, another non-sedating antihistamine, for their ability to inhibit the bronchial response to histamine and other autacoids which have been implicated as contributing to the symptoms of an allergic reaction. In addition, the two antihistamines were evaluated in models of immunologically mediated allergic reactions. Loratadine is a more potent inhibitor of histamine-induced bronchospasm in guinea pigs than is terfenadine. Both antihistamines exhibit marked antiserotonin activity at doses 10 times their antihistamine ED50 values. In contrast, loratadine and terfenadine produce little or no inhibition of the bronchial responses to methacholine, leukotriene C4 or platelet-activating factor. An allergic bronchospasm in guinea pigs is inhibited by loratadine (ED50 = 0.40 mg/kg, p.o.) and terfenadine (ED50 = 1.7 mg/kg, p.o.). The bronchospasm associated with allergic anaphylaxis in rats is significantly inhibited by 10 mg/kg, p.o. loratadine and 30 mg/kg, p.o. terfenadine. Loratadine exhibits antiallergy activity in vitro. At micromolar concentrations, loratadine inhibits the release of histamine from Con A and A23187-stimulated rat peritoneal mast cells and the release of histamine and leukotriene C4 from a Con A-stimulated cloned murine mast cell line.

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loratadine, Claritin
Loratadine, an antihistamine, blocks antigen-and ionophore-induced leukotriene release from human lung in vitro.

Temple DM, McCluskey M.

Department of Pharmacology, University of Sydney, Australia.

Some H1-antihistamines possess anti-allergic properties, and inhibit the immunological release of mediators including histamine and sulfiopeptide-leukotrienes (slow reacting substance of anaphylaxis) from lung. The effects of the antihistiamine loratadine, SCH29851, on the release of leukotrienes and histamine from human lung fragments were measured, using the calcium ionophore A23187 and an extract of antigen from Dermatophagoides pteronyssinus, house dust mite, (with passively sensitized lung) as releasing agents. Loratadine (1-20 microM) inhibited the release of leukotrienes in a concentration-dependent manner when release was induced by calcium ionophore from lung specimens from 8 subjects, and also when release was induced by antigen from lung specimens from 7 subjects. Histamine release was unaffected by these concentrations of loratadine in both types of experiment.

Online source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=2470117&dopt=Abstract loratadine, Claritin