loratadine, Claritin
Effects of nonsedating histamine H1-antagonists on EEG activity and behavior in the cat.

Marzanatti M, Monopoli A, Trampus M, Ongini E.

Research Laboratories, Essex Italia, Milan, Italy.

The central effects of the newly-developed antihistamines (H1-receptor antagonists) loratadine, astemizole, mequitazine and terfenadine were evaluated by studying brain electrical activity (EEG), sleep-waking patterns and behavior in the cat. The different stages of the sleep-waking cycle, i.e., wakefulness (W), spindle sleep (SS), slow wave sleep (SWS) and REM sleep (REM) were evaluated. The power spectrum analysis of the EEG was obtained by a computerized technique. For comparison, the sedating agent diphenhydramine was examined. Given at 3 mg/kg orally, a dose slightly above that effective therapeutically, diphenhydramine markedly affected behavior and all sleep stages. In particular, it depressed REM and increased SS (drowsiness). The EEG showed occasional spikes typical of subconvulsive states. Loratadine did not modify either sleep patterns or behavior over the 3-30 mg/kg dose range orally, which is far above that used clinically. The EEG, evaluated either visually or by spectral power analysis, was unaffected. Astemizole at 10 and 30 mg/kg PO reduced REM, markedly altered behavior at 30 mg/kg, but did not modify EEG activity. Mequitazine, at low doses (1-10 mg/kg PO), enhanced SS and decreased SWS and REM. Like diphenhydramine, mequitazine induced EEG changes typical of subconvulsive states and affected EEG power over the frequency range of 0.1-15.0 Hz. Terfenadine did not change sleep patterns and slightly affected behavior only at the high dose of 30 mg/kg orally; EEG activity was not influenced. These data show that: a) diphenhydramine and mequitazine appear to produce CNS effects by altering basic processes within the brain; b) astemizole and terfenadine seem to cross the blood-brain barrier at high doses only; c) loratadine has the lowest liability to produce central side effects. Of the sleep features examined, REM appeared to be the most sensitive stage to blockade of central H1-receptor pathways.

Online source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=2572005&dopt=Abstract loratadine, Claritin



loratadine, Claritin
Selective displacement of [3H]mepyramine from peripheral vs. central nervous system receptors by loratadine, a non-sedating antihistamine.

Ahn HS, Barnett A.

Displacement of [3H]mepyramine binding was compared in membranes from guinea-pig lung vs. cerebral cortex as a measure of affinity for peripheral vs. central nervous system (CNS) histamine receptors. Loratadine, a new non-sedating antihistamine, was found to be the only compound tested which was selective for lung (Ki = 35 nM) vs. cortex (Ki = 118 nM). This difference is statistically significant (P less than 0.05) whereas there was no significant (P greater than 0.05) difference in the Kis between the 2 tissues for terfenadine, astemizole, mequitazine or chlorpheniramine. It is concluded from these and other studies that the lack of significant sedative effects shown with loratadine is due to its poor penetration into the CNS and selectivity for peripheral histamine receptors.

Online source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=2875889&dopt=Abstract loratadine, Claritin



loratadine, Claritin
Studies on the central effects of the H1-antagonist, loratadine.

Bradley CM, Nicholson AN.

Effects of loratadine (10, 20 and 40 mg) on visuo-motor coordination, dynamic visual acuity, short-term memory, digit symbol substitution, and on subjective assessments of mood were tested before, and 0.5, 1.5, 3.5 and 5.5 h after ingestion by 6 healthy female adults. There were no effects of 10 or 20 mg loratadine. With 40 mg loratadine the number of substitutions on the digit symbol test was reduced 5.5 h after ingestion, and on dynamic visual acuity response time was increased at 3.5 h and the number of responses missed was increased at 5.5 h. Triprolidine (10 mg) which was used as active control impaired performance on all the tasks and impaired performance was observed at all times after ingestion. Loratadine is a promising antihistamine for individuals involved in skilled activity. The anticipated single daily dose of 10 mg is unlikely to impair performance.

Online source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=2886343&dopt=Abstract loratadine, Claritin



loratadine, Claritin
Sedation with "non-sedating" antihistamines: four prescription-event monitoring studies in general practice.

Mann RD, Pearce GL, Dunn N, Shakir S.

Southampton University, Southampton. DrMann manorcottage.fsbusiness.co.uk

OBJECTIVES: To investigate the frequency with which sedation was reported in post-marketing surveillance studies of four second generation antihistamines: loratadine, cetirizine, fexofenadine, and acrivastine. DESIGN: Prescription-event monitoring studies. SETTING: Prescriptions were obtained for each cohort in the immediate post-marketing period. SUBJECTS: Event data were obtained for a total of 43 363 patients. MAIN OUTCOME MEASURES: Reporting of sedation or drowsiness. RESULTS: The odds ratios (adjusted for age and sex) for the incidence of sedation were 0.63 (95% confidence interval 0.36 to 1.11; P=0.1) for fexofenadine; 2.79 (1.69 to 4.58; P<0.0001) for acrivastine, and 3.53 (2.07 to 5.42; P<0.0001) for cetirizine compared with loratadine. No increased risk of accident or injury was evident with any of the four drugs. CONCLUSIONS: Although the risk of sedation was low with all four drugs, fexofenadine and loratadine may be more appropriate for people working in safety critical jobs.

Online source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=10784544&dopt=Abstract loratadine, Claritin



loratadine, Claritin
Duration of the inhibitory activity on histamine-induced skin weals of sedative and non-sedative antihistamines.

Almind M, Dirksen A, Nielsen NH, Svendsen UG.

Medical Dept. TTA, State University Hospital, Copenhagen, Denmark.

The inhibitory effect of orally administered dexchlorfeniramine (4 mg/day), cyproheptadine (8 mg/day), astemizole (20 mg/day), loratadine (40 mg/day) and terfenadine (120 mg/day) on the size of histamine-induced weals was tested by skin prick test with histamine in an open study including 23 healthy individuals. The antihistamines were administered for 2 days in the nationally recommended therapeutic doses. For all drugs the maximal weal suppression with the dosage chosen was recorded the day after the last dosage, being 29% (for dexchlorfeniramine), 72% (for cyproheptadine), 50% (for astemizole), 62% (for loratadine), and 56% (for terfenadine) of the baseline value. For the drugs in the same order the duration of the inhibitory effect of the drugs after the last dose administered was between 3-4, 7-11, 17-28, 4-7, and 4-7 days, respectively.

Online source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=2905113&dopt=Abstract loratadine, Claritin



loratadine, Claritin
Loratadine: multiple-dose pharmacokinetics.

Radwanski E, Hilbert J, Symchowicz S, Zampaglione N.

Department of Drug Metabolism and Pharmacokinetics, Schering Corporation, Bloomfield, NJ 07003.

The steady-state pharmacokinetics of loratadine (L), a new long-acting antihistamine devoid of CNS activity, was investigated in 12 healthy male volunteers. Each volunteer received 40-mg L capsules q24h for ten days. Blood samples were collected at various times on day 1, 5, 7, and 10 and assayed for L by radioimmunoassay (RIA) and for descarboethoxyloratadine (DCL), a known active metabolite, by high-performance liquid chromatography (HPLC). The plasma L and DCL concentration-time data in the disposition phases were fitted to a biexponential equation for pharmacokinetic analysis. Steady-state plasma L Cmax concentrations were reached at 1.5 hour (Tmax) after each dose. DCL steady-state Cmax values ranged 26 to 29 ng/mL at a Tmax ranging from 1.8 to 3 hours. The AUC at steady state, AUC tau, was 80 to 96 and 349 to 421 h X ng/mL for L and DCL, respectively. The accumulation indexes (Ra) based on AUC tau ratios, did not change for either compound after day 5. Ra values for L and DCL after the fifth dose were 1.4 and 1.9, respectively, indicating that there is little accumulation of either L or DCL after a multiple (once-a-day) dosage regimen. The t1/2 beta at steady state were 14.4 and 18.7 hours for L and DCL, respectively, which were similar to those reported following a single-dose L administration. Observed plasma drug concentrations were in good agreement with predicted values derived for pharmacokinetic parameters.

Online source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=2958516&dopt=Abstract loratadine, Claritin