loratadine, Claritin
Sensitive gas-liquid chromatographic method for the determination of loratadine and its major active metabolite, descarboethoxyloratadine, in human plasma using a nitrogen-phosphorus detector.

Johnson R, Christensen J, Lin CC.

Wisconsin Analytical and Research Services, Madison 53713.

A sensitive gas-liquid chromatographic (GLC) method was developed for the determination of loratadine, a long-acting tricyclic antihistamine, and its active metabolite, descarboethoxyloratadine, in human plasma. The method involved extraction with organic solvent at neutral and alkaline pH. The organic layer from the neutral pH extraction was evaporated to dryness, reconstituted and injected into the GLC system. On the other hand, to the organic layer from the alkaline pH extraction trifluoroacetic anhydride was added. Following addition of H2O, the mixture was centrifuged and the organic layer was evaporated to dryness, reconstituted and injected onto the GLC system that was equipped with a nitrogen specific detector and a fused-silica capillary column. The linearity for both loratadine and descarboxyloratadine were demonstrated with r > or = 0.998 at concentrations ranging from 0.1 to 30 ng/ml. The results showed that the GLC method was accurate (bias < or = 12%) and precise (coefficient of variation, C.V., < or = 12%) for loratadine and descarboethoxyloratadine. The limit of quantitation was 0.1 ng/ml for loratadine with a C.V. of 9.2% and for descarboethoxyloratadine with a C.V. of 5.3%. The GLC method described has been demonstrated to be useful for the determination of loratadine and descarboethoxyloratadine in plasma samples of pediatric volunteers following oral administration of a single dose of 10 mg of loratadine syrup.

Online source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=7952058&dopt=Abstract loratadine, Claritin



loratadine, Claritin
[Comparison of the inhibition of the cutaneous histamine test by astemizole, loratadine, and terfenadine]

[Article in Spanish]

Rincon Castaneda C, Tapia Rodriguez S, Gonzalez Luna LI, Ortiz Ramirez M.

Centro Medico Nacional Torreon, IMSS, Coah.

This article reviews a study which included 40 patients from the allergy out-patient clinic and compared the reactions caused by three drugs in the dermal inhibition of histamine. All patients received subcutaneous histamine and were checked on different days. The size of the papule was compared before and after treatment. The reactions seen on day 20 were recorded and used for arriving at final conclusions. Astemizole showed better results than loratadine and terfenadine. Loratadine was seen to work better than terfenadine and the latter, better than the control group.

Online source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=8143023&dopt=Abstract loratadine, Claritin



loratadine, Claritin
Effects of loratadine on cytosolic Ca2+ levels and leukotriene release: novel mechanisms of action independent of the anti-histamine activity.

Letari O, Miozzo A, Folco G, Belloni PA, Sala A, Rovati GE, Nicosia S.

Institute of Pharmacological Sciences, University of Milan, Italy.

Loratadine, a non-sedating anti-histamine drug, displays in vitro potential anti-allergic properties not related to its interaction with the histamine H1 receptor. In a search for the mechanisms of these actions, we have found that loratadine induces an elevation of cytosolic calcium ion, [Ca2+]i, in rat peritoneal macrophages or human platelets. The mechanism of this elevation resides in the ability of loratadine to discharge intracellular Ca2+ stores, similarly to thapsigargin. This in turn brings about the inhibition of [Ca2+]i rise induced by physiological activators (platelet activating factor and ADP), as well as by thapsigargin. One of the active metabolites of loratadine, descarbo-ethoxy-loratadine, and another anti-histamine, namely terfenadine, exhibit the same effects. In addition, loratadine partially inhibits antigen-induced leukotriene release from human bronchi, but is unable to inhibit the concomitant contraction. We conclude that loratadine can interfere with the mechanisms controlling Ca2+ release, thus inhibiting the cell activation elicited by various agonists through [Ca2+]i elevation. This might be the mechanism underlying its anti-allergic actions in vitro. Furthermore, loratadine might represent an interesting tool in the study of Ca2+ homeostasis.

Online source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=8174605&dopt=Abstract loratadine, Claritin



loratadine, Claritin
Effect of loratadine on human eosinophil function in vitro.

Eda R, Sugiyama H, Hopp RJ, Bewtra AK, Townley RG.

Allergic Disease Center, Creighton University School of Medicine, Omaha, Nebraska.

We investigated the in vitro effect of loratadine, a new nonsedating H1 histamine antagonist, on the eosinophil functions of chemotaxis, superoxide anion (O2-) generation and eosinophil cationic protein (ECP) release, using purified eosinophils obtained from allergic patients. Loratadine significantly attenuated platelet-activating factor (PAF)-induced eosinophil chemotaxis and O2- generation at therapeutic concentrations (equivalent to serum concentrations after single oral administration of 20 mg or 40 mg). Loratadine, however, had no effect on PAF-induced ECP release. These findings suggest that loratadine has a direct inhibitory effect on eosinophil activation and may be beneficial in the therapy of allergic disorders with its anti-allergic properties.

Online source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=8214802&dopt=Abstract loratadine, Claritin



loratadine, Claritin
Pharmacological modulation of IL-6 and IL-8 secretion by the H1-antagonist decarboethoxy-loratadine and dexamethasone by human mast and basophilic cell lines.

Lippert U, Kruger-Krasagakes S, Moller A, Kiessling U, Czarnetzki BM.

Department of Dermatology, Virchow Klinikum, Humboldt Universitat, Berlin, Germany.

Mast cells and basophils are central effector cells of allergic reactions and are involved in inflammatory diseases. These cell types produce an array of mediators including a broad spectrum of cytokines. In order to examine whether antiallergic drugs modulate the release of these mediators, we have investigated the influence of dexamethasone and decarboethoxy-loratadine (DEL), the active metabolite of the H1-blocking agent loratadine, on the release of IL-6 and IL-8 by the human mast cell line HMC-1 and the human basophilic cell line KU812 by ELISA. Dexamethasone (10(-6)-10(-11) M) or Del (10(-5)-10(-14) M) were added to the cells either 1 h prior to or simultaneously with PMA and Ca-ionophore A23187. When preincubated with the cells, DEL dose-dependently suppressed IL-6 release by up to 40% and IL-8 release by up to 50%. Dexamethasone potently suppressed secretion of both cytokines if simultaneously added to the cells with the stimuli by up to 60% and after preincubation by up to 80%. Since both antihistamines and glucocorticoids are used for treatment of allergic diseases, the findings reported here indicate that these drugs may modulate allergic reactions via inhibition of cytokine release from mast cells and basophils.

Online source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=8528601&dopt=Abstract loratadine, Claritin



loratadine, Claritin
Antihistamine activity, central nervous system and cardiovascular profiles of histamine H1 antagonists: comparative studies with loratadine, terfenadine and sedating antihistamines in guinea-pigs.

Hey JA, Del Prado M, Cuss FM, Egan RW, Sherwood J, Lin CC, Kreutner W.

Schering-Plough Research Institute, Kenilworth, NJ, USA.

BACKGROUND: Sedation limits the clinical utility of classical H1 antihistamines, while newer antihistamines such as loratadine and terfenadine are non-sedating. However, clinical use of the terfenadine has been associated with rare but severe cardiac arrhythmias, in particular torsades de pointes. OBJECTIVE: To establish a quantitative experimental model for assessing the sedating and cardiotoxicity potential of non-sedating and sedating antihistamines. METHODS: Drugs were administered intravenously and the integrated amplitude of the cortical electroencephalogram (EEG) signal was recorded. The threshold dose that depressed EEG activity was compared with the dose required to inhibit by 50% the peripheral bronchospasm elicited by 10 micrograms/kg i.v., of histamine. In separate studies, the electrocardiogram (ECG) and cardiovascular effects of loratadine (30 and 100 mg/kg, i.v.), terfenadine (10 mg/kg, i.v.), promethazine (5 mg/kg, i.v.) and diphenhydramine (20 mg/kg, i.v.) were evaluated. RESULTS: The sedating antihistamines, diphenhydramine and promethazine, depressed the integrated EEG at doses between 0.6 and 2.0 times their peripheral antihistamine doses. Loratadine had no EEG depressant activity at 100 mg/kg, i.v., a dose more than 170 times its ED50 (0.58 mg/kg, i.v.) against histamine bronchospasm. We were unable to evaluate the EEG effects of terfenadine, because it produced cardiovascular collapse at 10 mg/kg, i.v. Loratadine and promethazine did not produce adverse cardiovascular effects, nor did they alter normal ECG activity. Diphenhydramine produced bradycardia followed by a transient hypertensive phase without affecting the QTc interval. In contrast, terfenadine elicited hypotension, bradycardia and significant arrhythmogenic activity, causing a prolongation of the QTc interval and a torsades de pointes--like ventricular arrhythmia. Pharmacokinetic studies after i.v. administration of loratadine (30 and 100 mg/kg) demonstrated plasma levels of loratadine and its major metabolite descarboethoxyloratadine to be several orders of magnitude greater than levels found in humans at the clinical dose of 10 mg. CONCLUSION: The CNS depressant effects of H1 antihistamines are promethazine approximately diphenhydramine >> loratadine = placebo. Of the non-sedating antihistamines, loratadine was devoid of adverse cardiovascular effects whereas terfenadine caused a pronounced disruption of the normal ECG, characterized by a torsades de pointes-like effect.

Online source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=8556569&dopt=Abstract loratadine, Claritin