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At least 19 recordsLinked to original sources
PubMed2001

Olopatadine ophthalmic solution adjunctive to loratadine compared with loratadine alone in patients with active seasonal allergic conjunctivitis symptoms.

BACKGROUND: Olopatadine ophthalmic solution 0.1% (Patanol, Alcon Laboratories, Fort Woth, TX) is approved for the treatment of the signs and symptoms of allergic conjunctivitis. Loratadine 10 mg (Claritin, Schering-Plough, Madison, NJ) is a nonsedating oral antihistamine approved for the treatment of the signs and symptoms of allergic rhinitis. OBJECTIVE: To compare the efficacy of olopatadine used adjunctively with loratadine versus loratadine alone in patients with seasonal allergic conjunctivitis. METHODS: This three-center, observer-masked, treatment-controlled, randomized, parallel-group study involved patients aged 7 to 74 years with seasonal allergic conjunctivitis. Patients were treated for 7 days with either olopatadine twice daily adjunctive to loratadine once daily or only loratadine once daily. Efficacy variables (ocular itching and redness, physician's impression, patient's impression, patient diary ratings of ocular redness and itching), and safety parameters were evaluated during the screening visit and on days 0, 3, and 7. Patients completed the rhinoconjunctivitis quality of life questionnaire on days 0 and 7. RESULTS: Ninety-four patients received study drug. Patients receiving olopatadine twice daily in addition to loratadine once daily exhibited less ocular itching (P = 0.0436) and rated their ocular condition as more improved compared with those receiving loratadine alone (P < 0.0022). Twenty minutes after initial dosing, olopatadine plus loratadine relieved ocular itching and redness significantly better than loratadine alone (P = 0.001). Both treatment groups showed clinically meaningful improvements in overall quality of life in all but one of the rhinoconjunctivitis quality of life questionnaire domains. Overall, and in most domains, olopatadine plus loratadine also provided significantly better (P < 0.05) quality of life than loratadine alone at day 7. CONCLUSIONS: Compared with loratadine alone, olopatadine adjunctive to loratadine provides greater relief of ocular itching and redness, a better quality of life, and is well tolerated in patients with seasonal allergic conjunctivitis.

Adolescent↗
PubMed1997

Loratadine and desethoxylcarbonyl-loratadine inhibit the immunological release of mediators from human Fc epsilon RI+ cells.

BACKGROUND: Loratadine, a novel histamine H1-receptor antagonist, is effective in the treatment of patients with seasonal and perennial rhinitis and some allergic skin disorders. Histamine and other chemical mediators are synthesized and immunologically released by human peripheral blood basophils and tissue mast cells (Fc epsilon RI+ cells). OBJECTIVE: To evaluate the effects of loratadine and its main metabolite, desethoxylcarbonyl-loratadine (des-loratadine), on the immunological release of preformed (histamine and tryptase) and de novo synthesized mediators (leukotriene C4: LTC4 and prostaglandin D2:PGD2) from human Fc epsilon RI+ cells. METHODS: Human Fc epsilon RI+ cells purified from peripheral blood and from skin (HSMC) and lung tissue (HLMC) were preincubated with loratadine and des-loratadine before immunological challenge with Der p 1 antigen or anti-Fc epsilon RI. The release of preformed mediators (histamine and tryptase) and de novo synthesized eicosanoids was evaluated in the supernatants of human Fc epsilon RI+ cells. RESULTS: Preincubation (15 min, 37 degrees C) of purified (36-74%) basophils with loratadine (3 x 10(-6)-10(-4)M) and des-loratadine before Der p 1 antigen or anti-Fc epsilon RI challenge concentration-dependently (5-40%) inhibited the release of histamine and LTC4. Loratadine (3 x 10(-6)-10(-4)M) and des-loratadine also inhibited (10-40%) histamine, LTC4, and PGD2 release from purified HLMC (16-68%) activated by anti-Fc epsilon RI. Loratadine (3 x 10(-6)-10(-4)M) and des-loratadine caused concentration-dependent inhibition (10-40%) of histamine, tryptase, LTC4, and PGD2 release from purified HSMC (24-72%) immunologically challenged with anti-Fc epsilon RI. CONCLUSION: These results indicate that loratadine and its main metabolite have anti-inflammatory activity by inhibiting the release of preformed and de novo synthesized mediators from human Fc epsilon RI+ cells.

Adult↗
PubMed2002

A comparative study of the side effects between pseudoephedrine in Loratadine plus Pseudoephedrine Sulfate Repetabs Tables and loratadine + pseudoephedrine tablet in treatment of allergic rhinitis in Thai patients.

The objective of the study was to evaluate the adverse reactions of Loratadine plus Pseudoephedrine Sulfate Repetabs Tables (LTD+PSE Repetabs) (Loratadine 5 mg + Pseudoephedrine 120 mg) twice daily with that of loratadine (5 mg) twice daily and pseudoephedrine (60 mg) quarter daily in the treatment of patients with allergic rhinitis. The study was designed as an investigator-blind, parallel group study. In this study, 56 patients were equally separated into 2 groups and treated for 14 days with either LTD+PSE Repetabs or loratadine + pseudoephedrine tablet. Both groups were comparable in age, gender, weight; baseline systolic blood pressure, diastolic blood pressure and pulse rate. The change of systolic blood pressure, diastolic blood pressure, and pulse rate did not reach clinical significance throughout the study period. There was no significant difference in occurrences of insomnia, palpitation, mouth dryness and anxiety. However, the incidence of patients with tremor at day 14 in the loratadine + pseudoephedrine tablet group was significantly higher than the LTD+PSE Repetabs group (39% vs 10.7%, p-value = 0.03). Furthermore, one patient in the loratadine + pseudoephedrine tablet group had to discontinue medication at day 7 due to insomnia. In conclusion, LTD+PSE Repetabs is well tolerated and has fewer adverse effects when compared to the loratadine + pseudoephedrine tablet.

Adolescent↗
PubMed2003

A sensitive LC/MS/MS method using silica column and aqueous-organic mobile phase for the analysis of loratadine and descarboethoxy-loratadine in human plasma.

A sensitive method using liquid chromatography with tandem mass spectrometric detection (LC/MS/MS) was developed and validated for the simultaneous analysis of antihistamine drug loratadine (LOR) and its active metabolite descarboethoxy-loratadine (DCL) in human plasma. Deuterated analytes, i.e. LOR-d(3) and DCL-d(3) were used as the internal standards (I.S.). Analytes were extracted from alkalized human plasma by liquid/liquid extraction using hexane. The extract was evaporated to dryness under nitrogen, reconstituted with 0.1% (v/v) of trifluoroacetic acid (TFA) in acetonitrile, and injected onto a 50 x 3.0 mm I.D. 5 microm, silica column with an aqueous-organic mobile phase consisted of acetonitrile, water, and TFA (90:10:0.1, v/v/v). The chromatographic run time was 3.0 min per injection and flow rate was 0.5 ml/min. The retention time was 1.2 and 2.0 min for LOR and DCL, respectively. The tandem mass spectrometric detection was by monitoring singly charged precursor-->product ion transitions: 383-->337 (m/z) for LOR, 311-->259 (m/z) for DCL, 388-->342 (m/z) for LOR-d(3), and 316-->262 (m/z) for DCL-d(3). The low limit of quantitation (LLOQ) was 10 pg/ml for LOR and 25 pg/ml for DCL. The inter-day precision of the quality control (QC) samples was 3.5-9.4% relative standard deviation (R.S.D.). The inter-day accuracy of the QC samples was 99.0-107.9% of the nominal values.

Chromatography, Liquid↗
PubMed2006

Evaluation of product switching after a state Medicaid program began covering loratadine OTC 1 year after market availability.

OBJECTIVE: The conversion of loratadine from prescription (Rx)-only to over-the-counter (OTC) status on November 27, 2002, brought about the question of how OTC products may influence utilization of both OTC and Rx-only low-sedating antihistamines (LSAs) simultaneously. North Carolina (NC) Medicaid initially did not cover loratadine OTC but subsequently changed the policy 1 year after OTC conversion, on November 23, 2003. The objective of this study was to determine patterns of LSA utilization in relation to changes in OTC availability and Medicaid coverage policy and to assess the rate of product switching associated with these policies. METHODS: Administrative pharmacy claims from the NC Medicaid population of approximately 1.1 million eligible recipients were used to study the 3 years of LSA use between July 1, 2001, and June 30, 2004. Two general methods were employed to evaluate the extent of product switching. First, monthly rates of incident use, new starts (i.e., no LSA use in the prior 12-month period) and product switching in time series were determined. These series were constructed to include a baseline period of no OTC availability, a period of OTC availability without coverage, and a period of OTC availability with coverage. Second, product switching was assessed through the use of rate-ratio calculations. Three equal 12-month periods were compared using rate ratios: (1) a baseline referent period (July 1, 2001, to June 30, 2002) during which loratadine OTC was not yet available, (2) a noncoverage period (July 1, 2002, to June 30, 2003) during which loratadine OTC was introduced to the market but not covered by NC Medicaid, and (3) a coverage period (July 1, 2003, to June 30, 2004). The primary comparison periods for the 3 years were the 5-month periods from February to June of each year. RESULTS: The use of individual drugs within the LSA class responded to coverage changes as expected, with alternative LSAs replacing loratadine use in the loratadine noncoverage period. Switching behavior for individual drugs within the LSA class was strongly associated with coverage changes. Recipients using loratadine were 2.16 times more likely to switch to an alternative Rx-only antihistamine in the noncoverage period (95% confidence interval [CI], 2.10-2.22) as compared with the baseline period. Yet they were only 1.11 times as likely not to use an Rx LSA during the last 5 months of the noncoverage period (95% CI, 1.09-1.13), as compared with the baseline period, suggesting minimal OTC uptake. The largest 12-month percentage increase in market share was observed for cetirizine (13.4%) although desloratadine accounted for the largest switch rate from loratadine at 3.10 (95% CI, 2.91-3.30), as compared with the baseline period, with a total market share increase of 7.8%. This suggests that new users of LSAs were most likely to initiate therapy with cetirizine, while existing loratadine users were most likely to switch to desloratadine. Compared with baseline switch rates, LSA users were only 0.34 (95% CI; 0.32-0.37) times as likely to switch to loratadine OTC from another (Rx-only) LSA during the subsequent OTC coverage period. LSA expenditure per member per month (PMPM) was essentially constant over time, at dollar 3.03 in the 5-month pre-OTC period, dollar 2.96 in the 5-month loratadine noncoverage period, and dollar 2.93 in the 5-month coverage period for loratadine OTC. Total LSA utilization increased slightly, from 1.37 days PMPM in the 5-month pre-OTC period to 1.41 in the 5-month loratadine noncoverage period and 1.45 in the 5-month coverage period for loratadine OTC. Loratadine OTC accounted for only 4.1% of the total LSA days of therapy and 4.2% of the LSA patients in the 5-month OTC coverage period from February to June 2004. CONCLUSION: Medicaid recipients switched to another covered (Rx) LSA when loratadine became available as an OTC and was not covered. After the subsequent policy change 1 year later to cover loratadine OTC, there was little switching to loratadine OTC. Though the average cost per LSA claim dropped dollar 4.15 (6.6%), from dollar 62.79 in the baseline period to dollar 58.64 in the OTC coverage period, time-series and rate-ratio results suggest that an additional dollar 6.01 (10.2%) could have been saved per LSA claim had OTC coverage been in effect at the time of the conversion of loratadine to OTC status. Although coverage of loratadine OTC offers a substantial cost-savings opportunity for the Medicaid program compared with Rx-only LSAs, not covering the OTC product immediately at the time of OTC availability contributed to (a) increased switching to Rx-only LSA products and (b) little use of loratadine OTC in the subsequent OTC coverage period.

Cetirizine↗
PubMed2000

Evaluation of the pharmacokinetics and electrocardiographic pharmacodynamics of loratadine with concomitant administration of ketoconazole or cimetidine.

AIMS: To evaluate whether ketoconazole or cimetidine alter the pharmacokinetics of loratadine, or its major metabolite, desloratadine (DCL), or alter the effects of loratadine or DCL on electrocardiographic repolarization in healthy adult volunteers. METHODS: Two randomized, evaluator-blind, multiple-dose, three-way crossover drug interaction studies were performed. In each study, subjects received three 10 day treatments in random sequence, separated by a 14 day washout period. The treatments were loratadine alone, cimetidine or ketoconazole alone, or loratadine plus cimetidine or ketoconazole. The primary study endpoint was the difference in mean QTc intervals from baseline to day 10. In addition, plasma concentrations of loratadine, DCL, and ketoconazole or cimetidine were obtained on day 10. RESULTS: Concomitant administration of loratadine and ketoconazole significantly increased the loratadine plasma concentrations (307%; 90% CI 205-428%) and DCL concentrations (73%; 62-85%) compared with administration of loratadine alone. Concomitant administration of loratadine and cimetidine significantly increased the loratadine plasma concentrations (103% increase; 70-142%) but not DCL concentrations (6% increase; 1-11%) compared with administration of loratadine alone. Cimetidine or ketoconazole plasma concentrations were unaffected by coadministration with loratadine. Despite increased concentrations of loratadine and DCL, there were no statistically significant differences for the primary electrocardiographic repolarization parameter (QTc) among any of the treatment groups. No other clinically relevant changes in the safety profile of loratadine were observed as assessed by electrocardiographic parameters (mean (90% CI) QTc changes: loratadine vs loratadine + ketoconazole = 3.6 ms (-2.2, 9.4); loratadine vs loratadine + cimetidine = 3.2 ms (-1.6, 7.9)), clinical laboratory tests, vital signs, and adverse events. CONCLUSIONS: Loratadine 10 mg daily was devoid of any effects on electrocardiographic parameters when coadministered for 10 days with therapeutic doses of ketoconazole or cimetidine in healthy volunteers. It is concluded that, although there was a significant pharmacokinetic drug interaction between ketoconazole or cimetidine and loratadine, this effect was not accompanied by a change in the QTc interval in healthy adult volunteers.

Adult↗
PubMed1988

Excretion of loratadine in human breast milk.

The excretion of loratadine, a new nonsedating antihistamine, into human breast milk was studied in six lactating nonpregnant volunteers. Each volunteer received one 40-mg loratadine capsule. Milk and blood were collected before and at specified times (to 48 hours) after dosing. Plasma and milk loratadine concentrations were determined by a specific radioimmunoassay, and those of an active but minor metabolite, descarboethoxyloratadine, by high performance liquid chromatography (HPLC). Breast milk concentration-time curves of both loratadine and descarboethoxyloratadine paralleled the plasma concentration-time curves. For loratadine, the plasma Cmax was 30.5 ng/mL at 1.0 hour after dosing and the milk Cmax was 29.2 ng/mL in the 0 to 2 hour collection interval. Through 48 hours, the loratadine milk-plasma AUC ratio was 1.2 and 4.2 micrograms of loratadine was excreted in breast milk, which was 0.010% of the administered dose. For descarboethoxyloratadine, the plasma Cmax was 18.6 ng/mL at 2.2 hours after dosing, whereas the milk Cmax was 16.0 ng/mL, which was in the 4 to 8-hour collection interval. Through 48 hours, the mean milk-plasma descarboethoxyloratadine AUC ratio was 0.8 and a mean of 6.0 micrograms of descarboethoxyloratadine (7.5 micrograms loratadine equivalents) were excreted in the breast milk, or 0.019% of the administered loratadine dose. Thus, a total of 11.7 micrograms loratadine equivalents or 0.029% of the administered dose were excreted as loratadine and its active metabolite. A 4-kg infant ingesting the loratadine and descarboethoxyloratadine excreted would receive a dose equivalent to 0.46% of the loratadine dose received by the mother on a mg/kg basis.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1995

Loratadine administered concomitantly with erythromycin: pharmacokinetic and electrocardiographic evaluations.

OBJECTIVE: To evaluate the effects of coadministration of loratadine and erythromycin on the pharmacokinetics and electrocardiographic repolarization (QTc) pharmacodynamics of loratadine and its metabolite descarboethoxyloratadine in healthy volunteers. METHODS: Twenty-four healthy volunteers were studied in a prospective, double-blind crossover design while confined in a Clinical Research Center. The primary pharmacodynamic end point of the study was the difference between baseline and day 10 mean QTc intervals obtained from surface electrocardiograms. Plasma concentrations of loratadine, descarboethoxyloratadine, and erythromycin were measured on treatment day 10 for pharmacokinetic analysis. Subjects received in random sequence the following three treatments for 10 consecutive days during three separate study periods: 10 mg loratadine every morning plus 500 mg erythromycin stearate every 8 hours, or 10 mg loratadine every morning plus placebo every 8 hours, or placebo every morning plus 500 mg erythromycin stearate. RESULTS: Concomitant administration of loratadine and erythromycin was associated with increased plasma concentrations of loratadine (40% increase in area under the plasma concentration-time curve [AUC]) and descarboethoxyloratadine (46% increase in AUC) compared with loratadine alone. Analysis of variance showed no difference between the treatment groups in effect on QTc intervals compared with baseline, and no significant change from baseline was observed. No clinically relevant changes in the safety profile of loratadine were observed, and there were no reports of sedation nor syncope. CONCLUSION: Although concomitant administration of loratadine and erythromycin was associated with increased plasma concentrations of loratadine and descarboethoxyloratadine, no clinically relevant changes in the safety profile of loratadine were observed. In this study, 10 mg loratadine administered orally for 10 consecutive days was well tolerated when coadministered with therapeutic doses of erythromycin stearate.

Adult↗
PubMed2000

The pharmacokinetics, electrocardiographic effects, and tolerability of loratadine syrup in children aged 2 to 5 years.

OBJECTIVE: We assessed the pharmacokinetics and tolerability of 5 mg loratadine syrup (1 mg/mL) in children aged 2 to 5 years. METHODS: Two studies were undertaken. A single-dose, open-label bioavailability study was performed to characterize the pharmacokinetic profiles of loratadine and its metabolite desloratadine. Plasma concentrations of loratadine and desloratadine were determined at 0, 1, 2, 4, 8, 12, 24, 48, and 72 hours after a single administration of 5 mg loratadine syrup to 18 healthy children (11 male, 7 female; 12 black, 5 white, 1 other; mean age +/- SD, 3.8 +/- 1.1 years; mean weight +/- SD, 17.4 +/- 4.4 kg). In addition, a randomized, double-blind, placebo-controlled, parallel-group study was performed to assess the tolerability of 5 mg loratadine syrup after multiple doses. Loratadine (n = 60) or placebo (n = 61) was given once daily for 15 days to children with a history of allergic rhinitis or chronic idiopathic urticaria. In the loratadine group, 27 boys and 33 girls (52 white, 8 black) were enrolled, with a mean age +/- SD of 3.67 +/- 1.13 years and a mean weight +/- SD of 17.2 +/- 3.8 kg. In the placebo group, 27 boys and 34 girls (53 white, 7 black, 1 Asian) were enrolled, with a mean age +/- SD of 3.52 +/- 1.12 years and a mean weight +/- SD of 17.3 +/- 2.9 kg. Tolerability was assessed based on electrocardiographic results, occurrence of adverse events, changes in vital signs, and results of laboratory tests and physical examinations. RESULTS: The peak plasma concentrations of loratadine and desloratadine were 7.78 and 5.09 ng/mL, respectively, observed 1.17 and 2.33 hours after administration of loratadine; the areas under the plasma concentration-time curve to the last quantifiable time point for loratadine and desloratadine were 16.7 and 87.2 ng x h/mL, respectively. Single and multiple doses were well tolerated, with no adverse events occurring with greater frequency after multiple doses of loratadine than after placebo. Electrocardiographic parameters were not altered by loratadine compared with placebo. There were no clinically meaningful changes in other tolerability assessments. CONCLUSION: Loratadine was well tolerated in this small, selected group of children aged 2 to 5 years at a dose providing exposure similar to that with the adult dose (ie, 10 mg once daily).

Anti-Allergic Agents↗
PubMed2003

Pregnancy outcome after gestational exposure to loratadine or antihistamines: a prospective controlled cohort study.

BACKGROUND: Loratadine is a second-generation histamine H(1)-receptor antagonist, used in the treatment of allergic conditions. No prospective controlled trials on loratadine in human pregnancy have been published to date. OBJECTIVE: To determine whether the use of loratadine or other antihistamines (OAH) is associated with an increased risk of major anomalies. METHODS: Callers who were counseled by the Israeli Teratogen Information Service in regard to loratadine or OAH exposure during pregnancy were prospectively collected and followed up. Pregnancy outcome was compared among three exposure groups: loratadine, OAH, and a control group of patients who were counseled for nonteratogenic exposure, nonteratogenic controls (NTC). The OAH included astemizole, chlorpheniramine, terfenadine, hydroxyzine, promethazine, and dimetindene. RESULTS: We followed up 210 pregnancies exposed to loratadine (77.9% in the first trimester) and 267 pregnancies exposed to OAH (64.6% in the first trimester) and compared pregnancy outcome with that of 929 NTC. The rate of congenital anomalies did not differ among the groups [loratadine: 4/175 (2.3%), OAH: 10/247 (4.0%), NTC: 25/844 (3.0%), P =.553, relative risk (RR), 0.77; 95% confidence interval (CI), 0.27 to 2.19, (loratadine vs NTC); RR, 0.56; 95% CI, 0.18 to 1.77, (loratadine vs OAH)]. The rate did not differ between those exposed to antihistamines in the first trimester and the control patients [loratadine: 1/126 (0.8%), OAH: 7/146 (4.8%), NTC: 25/844 (3.0%), P =.152, RR, 0.27; 95% CI, 0.04 to 1.94, (loratadine vs NTC); RR, 0.17; 95% CI, 0.02 to 1.33, (loratadine vs OAH)]. CONCLUSIONS: This study on the use of loratadine in human pregnancy suggests that this agent does not represent a major teratogenic risk. The study was powered to find a 3-fold increase in the overall rate of major anomalies.

Abnormalities, Drug-Induced↗
PubMed1992

Evaluation of loratadine as an inducer of liver microsomal cytochrome P450 in rats and mice.

The non-sedating anti-histamine, loratadine [ethyl 4-(8-chloro-5,6-dihydro-11H-benzo[5,6]-cyclohepta[1,2-b]pyridin- 11-ylidene-1-piperidinecarboxylate], was administered orally in the diet to mature male rats at dosages of 4, 10 and 25 mg/kg/day for 2 weeks. The effects of these treatments on liver microsomal cytochrome P450 were evaluated by immunochemical and biochemical techniques, and were compared with the effects of treating rats with three different inducers of cytochrome P450, namely phenobarbital, 3-methylcholanthrene and dexamethasone. Treatment of rats with loratadine caused a dose-dependent increase in the levels of P450 2B1 and 2B2, the major phenobarbital-inducible P450 enzymes, as determined by Western immunoblotting. At the highest dosage tested, loratadine was less effective than phenobarbital as an inducer of 2B1 and 2B2, although the induction of these proteins could be detected immunochemically even at the lowest dosage of loratadine tested. Consistent with these observations, treatment of rats with loratadine caused a dose-dependent increase in the rate of two reactions that are catalyzed predominantly by 2B1/2, namely testosterone 16 beta-hydroxylation and 7-pentoxyresorufin O-dealkylation. At the highest dosage tested, loratadine caused a 7.3- and 8.5-fold increase in the rate of testosterone 16 beta-hydroxylation and 7-pentoxyresorufin O-dealkylation, respectively, compared with a 22- and 45-fold increase caused by phenobarbital treatment. Treatment of rats with loratadine caused a 1.4- to 2.0-fold increase in the 2 beta-, 6 beta- and 15 beta-hydroxylation of testosterone, which was associated with a similar increase in the levels of immunoreactive P450 3A1 and/or 3A2. As an inducer of P450 3A1/2, loratadine was slightly less effective than phenobarbital, and was considerably less effective than dexamethasone, which caused a 10- to 33-fold increase in testosterone 2 beta-, 6 beta- and 15 beta-hydroxylase activity. At the dosages tested, loratadine did not increase the levels of P450 1A1, the major 3-methylcholanthrene-inducible P450 enzyme, as determined by Western immunoblotting. The rate of 7-ethoxyresorufin O-dealkylation, which is catalyzed predominantly by P450 1A1, increased 1.9-fold after loratidine treatment, but this increase was less than that caused by phenobarbital treatment (2.2-fold), and was considerably less than that caused by 3-methylcholanthrene treatment (33-fold). The effects of treating mature male mice with loratadine on liver microsomal cytochrome P450 resembled the effects observed in rats. These results indicate that loratadine is a phenobarbital-type inducer of liver microsomal cytochrome P450 in rats and mice.

Animals↗
PubMed2005

Suppression of the histamine-induced wheal and flare response by fexofenadine HCl 60 mg twice daily, loratadine 10 mg once daily and placebo in healthy Japanese volunteers.

BACKGROUND: The effects of the selective H1-receptor antagonist fexofenadine have been widely demonstrated in Western populations; however, to date, limited data comparing the effects of fexofenadine with other antihistamines have been reported in Japanese subjects. OBJECTIVE: To investigate the effect of fexofenadine and loratadine on the histamine-induced cutaneous wheal and flare response in healthy Japanese volunteers. METHODS: Eighteen healthy male and female Japanese volunteers aged 20-53 years were randomized to receive fexofenadine HCl 60 mg twice daily, loratadine 10 mg once daily or placebo in a 1-day, three-period, double-blind, crossover study. For each treatment, the wheal and flare response to 100 mg/mL histamine was assessed at baseline and at 1, 1.5, 2, 2.5, 3, 3.5, 4, 8, 12 and 24 hours post-dose. Blood samples were taken for pharmacokinetic analysis. RESULTS: Fexofenadine produced significantly greater percentage suppression of the overall wheal response compared with placebo and loratadine (43.1% versus 10.0% and 15.2%, respectively; p < 0.001). Similarly, fexofenadine significantly suppressed the overall flare response compared with placebo and loratadine (43.0% versus 3.5% and -8.9%, respectively; p < 0.01). Loratadine was statistically no different from placebo in terms of both overall wheal and flare suppression. Area under the curve analysis for wheal and flare reduction (0-12 hours post-dose) confirmed these findings. For wheal inhibition, fexofenadine had a significantly faster onset of action (defined as time to > or = 35% inhibition) compared with placebo (p < 0.001) and loratadine (p < 0.01); for flare, fexofenadine had a significantly faster onset of action than loratadine (p < 0.01). Mean maximum inhibition (the mean of the greatest inhibition achieved from baseline for each treatment) for wheal was achieved significantly faster with fexofenadine than loratadine (p < 0.01), and fexofenadine had a significantly longer duration of effect on suppressing wheal and flare compared with placebo and loratadine (p < 0.05 for all). The antihistamine effects of fexofenadine correlated significantly with its Cmax, while loratadine activity did not correlate significantly with its plasma levels. CONCLUSIONS: Fexofenadine is a potent suppressor of the histamine-induced wheal and flare response in healthy Japanese volunteers. These results support findings in Caucasian subjects, and confirm that fexofenadine has greater antihistaminergic activity than loratadine in this human model.

Adult↗
PubMed1998

A comparison of the efficacy of fluticasone propionate aqueous nasal spray and loratadine, alone and in combination, for the treatment of seasonal allergic rhinitis.

BACKGROUND: Intranasal corticosteroids and oral antihistamines are both effective in the treatment of seasonal allergic rhinitis, although the therapeutic value of administering the two types of agents concurrently has rarely been evaluated. This study was designed to compared the efficacy, safety, and impact on quality of life of fluticasone propionate aqueous nasal spray (FP ANS), loratadine, FP ANS plus loratadine, and placebo (an aqueous nasal spray plus tablet) in the treatment of seasonal allergic rhinitis during the mountain cedar allergy season in south central Texas. METHODS: Six hundred patients with seasonal allergic rhinitis were treated for 2 weeks with either FP ANS 200 microgram once daily, loratadine 10 mg once daily, the FP ANS and loratadine regimens combined, or placebo in a multicenter, randomized, double-blind, double-dummy, parallel-group study. RESULTS: Clinician- and patient-rated total and individual nasal symptom scores after 7 and 14 days of therapy and overall evaluations were significantly lower (P < .001) in the FP ANS and FP ANS plus loratadine groups compared with the loratadine only and placebo groups. Loratadine was not statistically different from placebo in clinician and patient symptom score ratings nor in overall clinician and patient evaluations. FP ANS plus loratadine and FP ANS monotherapy were comparable in efficacy in almost all evaluations; for some patient-rated symptoms the combination was found superior. Mean score changes in the Rhinoconjunctivitis Quality of Life Questionnaire from baseline to day 14 showed significantly greater improvement (P < .001) in quality of life in the FP ANS group than in the group of patients receiving loratadine only or placebo and no significant benefit was demonstrated in the FP ANS plus loratadine group over the FP ANS monotherapy group. No serious or unusual drug-related adverse events were reported. Combining loratadine with FP ANS did not alter the adverse events profile or frequency.

Administration, Intranasal↗
PubMed1999

Efficacy and safety of mizolastine 10 mg in a placebo-controlled comparison with loratadine in chronic idiopathic urticaria: results of the MILOR Study.

BACKGROUND: Mizolastine is a novel histamine H1-antagonist registered in Europe for the management of allergic rhinitis and urticaria. OBJECTIVES: To compare the clinical efficacy and safety of mizolastine with loratadine and placebo in patients with chronic idiopathic urticaria (CIU). METHODS: A multicentre, double-blind, parallel group study was designed in which 247 patients with CIU were randomised after a 1-week placebo run-in period to 10 mg daily mizolastine (n = 88), 10 mg daily loratadine (n = 79), or placebo (n = 80) for a 4-week treatment period. RESULTS: Mizolastine and loratadine both relieved symptoms of CIU. After 2 weeks' treatment, the severity of pruritus (visual analogue score (VAS) assessed by patients) decreased significantly in both the mizolastine and loratadine groups compared with placebo (mizolastine: -36.7 mm, P = 0.0001; loratadine: -29.8, P = 0.0071; placebo: -16.3); this improvement with both active treatments was maintained throughout the treatment period, the difference being significant only for the mizolastine group (P = 0.0090). Both active treatments were also associated with reduced weekly episodes of urticaria compared with placebo, which was significant after 2 weeks' treatment (mizolastine: 7.9 episodes, P = 0.0061; loratadine: 8.3, P = 0.0221; placebo: 13.3). Angioedema was improved to a clinically significant extent with mizolastine, and loratadine compared with placebo in those patients who had this symptom before treatment. Overall tolerability of both treatments was similar to placebo, and there were no clinically relevant effects on cardiac repolarisation with either mizolastine or loratadine. CONCLUSION: Mizolastine (10 mg daily) is confirmed as an effective and well tolerated agent, comparable to loratadine and superior to placebo, for the management of CIU. Mizolastine acted as rapidly as loratadine in improving urticarial symptoms from the first day of treatment.

Adult↗
PubMed1990

Pharmacokinetics of loratadine in patients with renal insufficiency.

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.

Adult↗
PubMed2006

The relative bioavailability of loratadine administered as a chewing gum formulation in healthy volunteers.

OBJECTIVE: The aim of this study was to investigate the pharmacokinetics of loratadine and its active metabolite desloratadine after single-dose administration of loratadine as a conventional tablet, orally disintegrating tablet (smelt tablet) and a chewing gum formulation with and without the collection of saliva. METHODS: Twelve healthy male volunteers participated in a four-period cross-over trial evaluating the effect of dosage forms on the pharmacokinetics of a single dose of loratadine. Loratadine was administered as two 10-mg conventional tablet, two 10-mg smelt tablet, a 30-mg portion of medicated chewing gum without collection of saliva and a 30-mg portion of medicated chewing gum with collection of saliva. Blood samples were taken at predefined sampling points 0-24 h after medication, and the plasma concentrations of loratadine and desloratadine were determined by high-performance liquid chromatography. Each study period was separated by a wash-out period of at least 7 days. RESULTS: The mean dose-corrected area under the plasma concentration-time curve extrapolated to infinity AUC(0-infinity) for the chewing gum formulation was statistically significantly increased compared to the tablet formulation (geometric mean ratio: 2.68; 95%CI: 1.75-4.09). Desloratadine pharmacokinetic parameters from the chewing gum formulation were not statistically significantly different from the conventional tablet. Neither loratadine nor desloratadine pharmacokinetics of the smelt tablet formulation were statistically significantly different from the conventional tablet formulation. Plasma concentrations of desloratadine following the administration of loratadine as chewing gum with saliva collection were very low. CONCLUSION: Our study showed that formulation of loratadine as a medicated chewing gum results in an almost threefold increase in relative bioavailability. This is most likely due to a bypass of first-pass metabolism as this study suggests that approximately 40% of the absorbed loratadine was absorbed via the oral mucosa.

Adsorption↗
PubMed1996

Identification of human liver cytochrome P450 enzymes that metabolize the nonsedating antihistamine loratadine. Formation of descarboethoxyloratadine by CYP3A4 and CYP2D6.

[3H]Loratadine was incubated with human liver microsomes to determine which cytochrome P450 (CYP) enzymes are responsible for its oxidative metabolism. Specific enzymes were identified by correlation analysis, by inhibition studies (chemical and immunoinhibition), and by incubation with various cDNA-expressed human P450 enzymes. Descarboethoxyloratadine (DCL) was the major metabolite of loratadine detected following incubation with pooled human liver microsomes. Although DCL can theoretically form by hydrolysis, the conversion of loratadine to DCL by human liver microsomes was not inhibited by the esterase inhibitor phenylmethylsulfonyl fluoride (PMSF), and was dependent on NADPH. A high correlation (r2 = 0.96, N = 10) was noted between the rate of formation of DCL and testosterone 6 beta-hydroxylation, a CYP3A-mediated reaction. With the addition of ketoconazole (CYP3A4 inhibitor) to the incubation mixtures, the residual rate of formation of DCL correlated (r2 = 0.81) with that for dextromethorphan O-demethylation, a CYP2D6 reaction. Rabbit polyclonal antibodies raised against the rat CYP3A1 enzyme (5 mg IgG/nmol P450) and troleandomycin (0.5 microM), a specific inhibitor of CYP3A4, decreased the formation of DCL by 53 and 75%, respectively, when added to 1.42 microM loratadine microsomal incubations. Quinidine (5 microm), a CYP2D6 inhibitor, inhibited the formation of DCL approximately 20% when added to microsomal incubations of loratadine at concentrations of 7-35 microM. Incubation of loratadine with cDNA-expressed CYP3A4 and CYP2D6 microsomes catalysed the formation of DCL with formation rates of 135 and 633 pmol/min/nmol P450, respectively. The results indicated that loratadine was metabolized to DCL primarily by the CYP3A4 and CYP2D6 enzymes in human liver microsomes. In the presence of a CYP3A4 inhibitor, loratadine was metabolized to DCL by the CYP2D6 enzyme. Conformational and electrostatic analysis of loratadine indicated that its structure is consistent with substrate models for the CYP2D6 enzyme.

Anti-Bacterial Agents↗