Loratadine Research Articles

LC-ESI-MS/MS estimation of loratadine-loaded self-nanoemulsifying drug delivery systems in rat plasma: Pharmacokinetic evaluation and computer simulations by GastroPlus™

A rapid, sensitive, and accurate bioanalytical method was established for the quantitation and pharmacokinetic investigation of loratadine (LTD) in rat plasma by liquid chromatography–electrospray ionization mass spectrometry (LC-ESI-MS/MS) using loratadine-d5 as internal standard (ISTD). The analyte and ISTD were extracted by solid-phase extraction and chromatographic separation was achieved on Gemini NX- Reverse Phase C18 (50×4.6mm;5μ) using mobile phase mixture of 5mM ammonium formate buffer in water (pH 3.5±0.1 with formic acid), and acetonitrile (20:80v/v), at a flow rate of 0.400mL/min with injection volume of 10μL. LTD and ISTD were detected at m/z 383.3→337.4 and 388.4→337.3 with retention time of 2.62 and 2.59min, respectively. High sensitivity (1.0ng/mL) was achieved using small volume of rat plasma (20μL) and the method was validated over a linearity range of 1.05–405.41ng/mL with high correlation coefficient (r=0.9998). The extraction method displayed a mean process efficiency of 63.25 and 65.47% for LTD and ISTD, respectively. The validated method when successfully applied for quantification of LTD in rat plasma revealed enhanced bioavailability of orally administered LTD-loaded self-nanoemulsifying drug delivery system (SNEDDS) (Cmax, 466.65±18.94ng/mL and AUC0-t 633.00±12.44 ng-h/mL) over LTD-suspension (Cmax, 104.75±2.87ng/mL and AUC0-t 287.00±9.11 ng-h/mL). The in vivo-in silico prediction by the GastroPlus™ software showed good prediction accuracy for LTD-SNEDDS (fold error<2). The Loo-Reigelman method (2-compartment) presented best model-fitting indicating adequate in vitro–in vivo correlations. Conclusively, the developed sensitive analytical method displayed enhanced systemic availability of LTD-SNEDDS, and the in vivo in silico approach revealed sufficiently good GI simulation.

HPTLC Method for the Determination of Paracetamol, Pseudoephedrine and Loratidine in Tablets and Human Plasma.

A sensitive, accurate and selective high performance thin layer chromatography (HPTLC) method was developed and validated for the simultaneous determination of paracetamol (PAR), its toxic impurity 4-aminophenol (4-AP), pseudoephedrine HCl (PSH) and loratidine (LOR). The proposed chromatographic method has been developed using HPTLC aluminum plates precoated with silica gel 60 F254 using acetone-hexane-ammonia (4:5:0.1, by volume) as a developing system followed by densitometric measurement at 254 nm for PAR, 4-AP and LOR, while PSH was scanned at 208 nm. System suitability testing parameters were calculated to ascertain the quality performance of the developed chromatographic method. The method was validated with respect to USP guidelines regarding accuracy, precision and specificity. The method was successfully applied for the determination of PAR, PSH and LOR in ATSHI(®) tablets. The three drugs were also determined in plasma by applying the proposed method in the ranges of 0.5-6 µg/band, 1.6-12 µg/band and 0.4-2 µg/band for PAR, PSH and LOR, respectively. The results obtained by the proposed method were compared with those obtained by a reported HPLC method, and there was no significance difference between both methods regarding accuracy and precision.

Non-Aqueous Titrimetric Assay for Determination of Loratadine in Pharmaceutical Preparations

Non-aqueous titrations is the most titrimetric procedure used in pharmacopoeial assays and serves a double purpose, as it suitable for the titration of weak acids and bases and provides a solvent in which organic compounds are soluble. A simple, cost-effective, rapid, and precise method for determination of loratadine (LOR) in pure and pharmaceutical dosage forms was developed. The method based on non-aqueous titration using acetous perchloric acid as a titrant and acetous crystal violet as indicator. All measurements are carried out by running simultaneous blank determinations and the final titer values are subtracted from blank to get actual amount of acetous perchloric acid equivalent to LOR. The method was successfully applied for determination of LOR in pure and some pharmaceutical preparations. The percentage recoveries of the proposed method were ranged from 84.8 ± 0.1% to 100.9 ± 0.1%. The method showed an acceptable precision and accuracy as it able to determine LOR in presence of the different excipients present in some commercial preparations without any significant interference.

UV-Vis Spectrophotometry and Multivariate Calibration Method for Simultaneous Determination of Theophylline, Montelukast and Loratadine in Tablet Preparations and Spiked Human Plasma.

Resolution of binary mixtures of theophylline (THEO), montelukast (MKST) and loratadine (LORA) with minimum sample pre-treatment and without analyte separation has been successfully achieved by multivariate spectrophotometric calibration, together with partial least-squares (PLS-1), principal component regression (PCR) and hybrid linear analysis (HLA). Data of analysis were obtained from UV-Vis spectra of three compounds. The method of central composite design was used in the ranges of 2-14 and 3-11 mg L-1 for calibration and validation sets, respectively. The models refinement procedure and their validation were performed by cross-validation. The minimum root mean square error of prediction (RMSEP) was 0.173 mg L-1 for THEO with PCR, 0.187 mg L-1 for MKST with PLS1 and 0.251 mg L-1 for LORA with HLA techniques. The limit of detection was obtained 0.03, 0.05 and 0.05 mg L-1 by PCR model for THEO, MKST and LORA, respectively. The procedure was successfully applied for simultaneous determination of the above compounds in pharmaceutical tablets and human plasma. Notwithstanding the spectral overlapping among three drugs, as well as the intrinsic variability of the latter in unknown samples, the recoveries are excellent.

THE PREPARATION AND SOLUBILITY OF LORATADINE-FUMARIC ACID BINARY MIXTURE

ABSTRACTObjective: Loratadine (LOR) is a biopharmaceutics classification system Class II drug that has low solubility and high permeability, so its absorptionrate is determined by the dissolution rate. The aim of this study was to prepare an LOR-fumaric acid (LOR-FUM) binary mixture and to investigate itsinfluence on the solubility and dissolution rate of LOR.Methods: LOR-FUM binary mixture was prepared by the wet grinding method in an equimolar ratio by the addition of two drops of methanol.Characterization of LOR-FUM binary mixture was conducted by the construction of the phase solubility, powder X-ray diffractometry, Fouriertransforms infrared spectroscopy, and polarizing microscopy methods. Solubility test was performed in water at room temperature, whereas thein vitro dissolution test was performed in the pH 1.2, 4.5, and 6.8 buffer solutions.Results: The phase solubility curve of LOR in FUM solution is similar to type B. The powder X-ray diffraction results show the crystallinity of LOR waschanged become more amorphous indicating the salt formation. Fourier transforms infrared spectroscopy (FTIR) spectra of LOR-FUM binary mixtureshowed the vibration peaks of an imine group on the pyridine ring of LOR and carbonyl group on the FUM are not detected. On the other hand, thepolarizing microscope images showed the crystal habit of LOR-FUM binary mixture after recrystallized from methanol contrast to crystal habit ofits pure components. The solubility in water of LOR-FUM binary mixture was higher than pure LOR. Amount of LOR released from LOR-FUM binarymixture in pH 4.5 and 6.8 buffer solutions was faster than from pure LOR.SConclusion: A binary mixture of LOR and FUM may improve the solubility and dissolution rate of LOR.Keywords: Loratadine, Fumaric acid, Binary mixture, Solubility, Dissolution rate.

Comparison of oral acrivastine versus loratadine for the treatment of chronic urticaria

Objective To compare the efficacy of oral acrivastine versus loratadine for the treatment of chronic urticaria. Methods Totally, 110 patients with chronic urticaria were randomly divided into 2 groups: acrivastine group (n = 56) treated with oral acrivastine capsules 8 mg thrice a day for 28 days, loratadine group (n = 54) treated with oral loratadine tablets 10 mg once every day for 28 days. Therapeutic effects were evaluated on day 7, 14 and 28 after the start of treatment. Results No significant differences were observed in the total response rate between the acrivastine group and loratadine group (73.5% (25/34) vs. 67.6% (25/37), P> 0.05), but the proportion of unresponsive patients was significantly lower in the acrivastine group than in the loratadine group (5.9% (2/34) vs. 32.4% (12/37), P 0.05). Conclusion Acrivastine is safe and effective for the treatment of chronic urticaria. Key words: Urticaria; Treatment outcome; Comparative effectiveness research; Acrivastine; Loratadine

Determination of Some Non-sedating Antihistamines via Their Native Fluorescence and Derivation of Some Quantitative Fluorescence Intensity - Structure Relationships.

A validated simple, novel, and rapid spectrofluorimetric method was developed for the determination of some non-sedating antihistamines (NSAs); namely cetirizine (CTZ), ebastine (EBS), fexofenadine (FXD), and loratadine (LOR). The method is based on measuring the native fluorescence of the cited drugs after protonation in acidic media and studying their quantitative fluorescence intensity - structure relationships. There was a linear relationship between the relative fluorescence intensity and the concentration of the investigated drug. Under the optimal conditions, the linear ranges of calibration curves for the determination of the studied NSAs were 0.10-2.0, 0.20-6.0, and 0.02-1.0 [Formula: see text] for (CTZ, FXD), (EBS), and (LOR); respectively. The factors affecting the protonation of the studied drugs were carefully studied and optimized. The method was validated according to ICH guidelines. The suggested method is applicable for the determination of the four investigated drugs in bulk and pharmaceutical dosage forms with excellent recoveries (97.67-103.80%). Quantitative relationships were found between the relative fluorescence intensities of the protonated drugs and their physicochemical parameters namely: the pKa, log P, connectivity indexes (χ(v)) and their squares. Regression equations (76) were obtained and not previously reported. Six of these equations were highly significant and used for the prediction of RFI of the studied NSAs.

Therapeutic effects of hydroxychloroquine combined with butyli flufenamatum ointment and other drugs for the treatment of polymorphous light eruption: a comparison study

Objective To evaluate the efficacy and safety of hydroxychloroquine combined with butyli flufenamatum ointment and other drugs for the treatment of polymorphous light eruption (PLE). Methods A total of 48 patients with PLE were randomly and equally classified into group 1 and group 2. Both groups took hydroxychloroquine 200 mg twice a day and loratadine 10 mg per day for the initial 4 weeks, then took hydroxychloroquine 100 mg twice a day alone for another 4 weeks. Group 1 also topically applied butyli flufenamatum ointment twice a day during the 8 weeks, while group 2 applied mometasone furoate cream twice a day for the first 2 weeks followed by butyli flufenamatum ointment twice a day for another 6 weeks. Each treatment cycle lasted 2 weeks, and both groups received 4 cycles of treatment. Patients were evaluated for the response rate at the end of each cycle, and for the total symptom score and erythema score before and after the 8-week treatment. Statistical analysis was carried out using t test, chi-square test, Fisher's exact test and repeated-measures analysis of variance with the SPSS17.0 software. Results On day 14, 28, 42 and 56, the total score improved in 0, 3, 12 and 19 patients in group 1 respectively, and in 1, 4, 12 and 20 patients in group 2 respectively; the erythema score improved in 1, 5, 13 and 18 patients in group 1 respectively, and in 0, 5, 11 and 17 patients in group 2 respectively. No significant difference was observed between the two groups in response rates at any of the above four time points (P > 0.05). Both the total score and erythema score significantly decreased after the 8-week treatment in both groups compared with the pretreatment scores (both P < 0.05). No serious adverse reaction was observed in either of the two groups. Conclusions Hydroxychloroquine combined with loratadine and butyli flufenamatum ointment shows high efficacy and safety for the treatment of PLE. Topical butyli flufenamatum ointment is highly effective for the treatment of PLE, especially for PLE cases mainly presenting with erythema. Key words: Hydroxychloroquine; Loratadine; Flufenamate acid; Treatment outcome; Comparative effectiveness research; Erythema; Polymorphic sun light eruption

Effect of Poloxamer on release of poorly water soluble drug Loratadine from solid dispersion: Kneading method

The main objective of the current study was to enhance the solubility and dissolution of poorly water soluble drug Loratadine (LOR) through formulation of solid dispersion systems (SDs) using hydrophilic polymers. SDs were prepared by kneading method using different drug-to-polymer ratios (1:3 and 1:5) with poloxomer 188 (samples DS1, DS2) and poloxomer 407 (samples DS3, DS4) as hydrophilic polymers. In vitro drug release studies were performed on prepared SDs (DS1-DS4) and compared to pure drug (LOR only, sample DS0). Prepared SDs showed significant improvement in the release profile compared to LOR.

Photostability of Loratadine Inclusion Complexes with Natural Cyclodextrins

The purpose of this study was to evaluate the photostability of inclusion complexes of the histamine antagonist loratadine (LORA) withα-,β-, andγ-cyclodextrins (CDs). Accordingly, binary drug-CD complexes were prepared using the coevaporation method at 1 : 1, 1 : 2, and 1 : 3 stoichiometric ratios, which were characterized by thermal analysis. Subsequently, solutions of the complexes at 500 μg mL−1in HCl 0.1 M were subjected to irradiation in a photostability chamber for 12 hours, and the content of the remaining active ingredient was quantified by means of high-performance liquid chromatography. It is possible to observe the presence of two products originating from photodegradation (P1 and P2), which were identified in solutions of loratadine withα- andβ-CD. By means of statistical analysis, we conclude that the drug:α-CD and drug:γ-CD (1 : 1) complexes proved to be more efficient in the photostability assay, obtaining a nonsignificant level of degradation and full recovery of LORA.

An investigation into the comparison of three human immunodeficiency virus (HIV) drug resistance interpretation algorithms

Human immunodeficiency virus (HIV) drug resistance is caused by mutations in the patient’s human immunodeficiency virus genome that renders antiretroviral (ARV) drugs less effective. Drug resistance not only results in the patient being more vulnerable to opportunistic infections, but also may increase the spread of resistant strains of HIV. Interpretation computer algorithms may be used to determine which ARV drug(s) the patient are resistant to, by analyzing the mutations that occurred in the patient’s HIV genome, instead of using expensive time consuming phenotypic laboratory tests. There are many different interpretation algorithms, but they often provide different resistance measures, even if applied to the same resistance profile. The aim of this study was to compare the latest versions of three HIV drug resistance interpretation algorithms in order to determine the extent of discrepancies between them. 2926 protease and 1981 reverse transcriptase subtype B sequences where obtained from the Stanford HIV-db genotype-phenotype correlation database. These sequences were pre-processed and the latest rules of the ANRS, HIV-db and REGA algorithms applied to them. The results were then compared with each other. These results indicate that although the accuracy of REGA, ANRS and HIV-db are similar, a deeper analysis of the results indicates that the interpretation algorithms are different. There need to be a mechanism of providing a single interpretation for a resistance profile of a genome. This may be created by collating the strengths of each of the interpretation algorithms. Key words: Bioinformatics, human immunodeficiency virus (HIV), REGA, Agence Nationale de Recherches sur le SIDA (ANRS), HIV-db, genotype, interpretation algorithms.

Solid Lipid Nanoparticles and Nanostructured Lipid Carriers of Loratadine for Topical Application: Physicochemical Stability and Drug Penetration through Rat Skin

Purpose: To prepare solid lipid nanoparticles (SLN) and nanostructured lipid carriers (NLC) of loratadine (LRT) for the treatment of allergic skin reactions. Methods: SLN and NLC were prepared by high pressure homogenization method. Their entrapment efficiency (EE) and loading capacity (LC) were determined. The physical stability of nanoparticles was investigated during 6 months of storage at room temperature (RT), 4 and 40 o C. Fourier transform infrared spectroscopy (FTIR), differential scanning calorimetry (DSC) and laser diffraction (LD) were used for the investigation of drug:excipient compatibility, thermal behaviour and particle size of the nanoparticles. In vitro release and ex vivo skin penetration of LRT were studied. Nanoemulsions (NE) were also prepared and characterized for comparison. Results: Nanoparticles sizes ranged from 0.222 ± 0.011 μm to 0.252 ± 0.014 μm (D50 as a value based on the volume distribution, the maximum particle diameter below which 50 % of the sample volume exists) They were obtained with high drug payloads (> 90.67 %). LRT was compatible with the other excipients after 6 months. Particle size did not significantly alter particularly at RT. The highest release rate was obtained with NE (1.339 ± 0.026 mcg/ml/h) followed by NLC (1.007 ± 0.011 mcg/ml/h) and SLN (0.821 ± 0.012 mcg/ml/h), indicating anomalous transport (p 0.05). NE showed the highest penetration rate (0.829 ± 0.06 mcg/cm 2 /h) (p < 0.05). Conclusion: SLN and NLC of LRT are alternative formulations for immediate treatment of allergic skin reactions with prolonged drug delivery via reservoir action. Keywords : Loratadine, Transdermal delivery, Controlled drug delivery, Solid Lipid nanoparticles, Nanostructured lipid carriers, Allergy

Meta-analysis of leukotriene receptor antagonist montelukast in the treatment of allergic rhinitis

To evaluate the treatment outcomes of leukotriene receptor antagonists (LTRA) as monotherapy or combined with the second-generation oral H1-histamines in the treatment of allergic rhinitis (AR), and to provide a basis for optimizing clinical therapeutic strategies. PubMed,EMBASE, CBMdisc and CJFD databases, retrieving randomized controlled trials (RCTs) of AR therapy literatures were searched. Based on the literature inclusion and exclusion criteria, the related literatures were selected and the quality was evaluated by using the Jadad scale. Meta-analysis was performed by Stata 12.1 software.For continuous outcomes, the weighted mean difference (WMD) and its 95% confidence intervals (CI) were calculated. The forest plots were drawn. The treatment outcomes included daytime nasal symptom scores (DNSS), nighttime symptom scores (NSS), composite symptom scores (CSS), daytime eye symptom scores (DESS), and the rhinoconjunctivitis quality of life questionnaire (RQLQ) were used to evaluate the therapeutic effects of LTRA on seasonal and perennial AR. Eleven of clinical RCTs including 14 809 cases of AR patients, aged 15 to 85 years old, were available for Meta-analysis. Montelukast, a drug of LTRA, was primarily evaluated in the study. The results of Meta-analysis showed: (1) Compared with the placebo, montelukast statistically significantly reduced the DNSS,NSS, CSS, and RQLQ scores in patients with seasonal and perennial AR, as well as the DESS in patients with seasonal AR.(2) There were no statistical differences in the improvement of the CSS,DESS, and RQLQ scores in patients with seasonal AR after the treatment by montelukast compared with loratadine, a second-generation oral H1-histamine.(3) Montelukast statistically significantly reduced the NSS, but not DNSS, in patients with seasonal AR compared with loratadine.(4) The combination therapy of montelukast and loratadine statistically significantly improved the CSS compared with either montelukast or loratadine monotherapy. Montelukast, a representative drug of LTRA, can be used as first-line therapy for AR, with comprehensive improvement of the nasal and ocular symptoms and the quality of life in AR patients. Montelukast combined with loratadine can significantly improve the diurnal and nocturnal symptoms for patients with seasonal AR, and the curative effect is better than the single use of montelukast or loratadine.

Expressions of interleukin-25 and interleukin-33 in peripheral blood of patients with chronic urticaria and their significance

Objective To detect the expression levels of interleukin (IL)-25 and IL-33 in peripheral blood of patients with chronic urticaria.Methods Ninety-three patients with chronic urticaria were included in this study along with 30 healthy individuals.All the patients were treated with loratadine for four weeks.Blood samples were collected from the healthy controls and patients before and after the four-week treatment.Enzyme-linked immunosorbent assay (ELISA) was performed to detect the serum levels of IL-25 and IL-33.The relationship between the expression levels of the two cytokines and urticaria severity was analyzed.Results The serum levels of IL-25 and IL-33 in the patients before treatment were significantly higher than those in the healthy controls (IL-25,139.86 ± 28.48 vs.114.41 ± 34.00 ng/L,P ＜ 0.01; IL-33,91.95 ± 21.88 vs.79.80 ± 30.72 ng/L,P ＜ 0.05),and positively correlated with the severity of urticaria (r =0.38,0.42,respectively,both P ＜ 0.01).After four weeks of treatment,clinical improvement was observed in 81.72％ of these patients with a significant decrease in the serum IL-25 level (116.48 ± 21.94 vs.139.86 ± 28.48 ng/L,P ＜ 0.01),but no obvious changes in the serum IL-33 level (90.88 ± 20.62 vs.91.95 ± 21.88 ng/L,P ＞ 0.05) compared with those before treatment.Conclusions The expressions of IL-25 and IL-33 are elevated in peripheral blood of patients with chronic urticaria,and positively correlated with the severity of urticaria. Key words: Urticaria; Interleukin-25; Interleukin-33; Loratadine

Investigation of cytotoxic and genotoxic effects of the antihistaminic drug, loratadine, on human lymphocytes

Context: Loratadine (LOR) is a new generation antihistamine used in the treatment of allergic disorders. Objective: The aim of this study was to evaluate the cytogenotoxic effect of LOR on human peripheral blood lymphocytes. Materials and methods: We investigated the genotoxic effect of this drug in cultured human peripheral blood lymphocytes using sister chromatid exchange (SCE), chromosomal aberrations (CA) and micronucleus (MN) assay in culture conditions. Proliferation index (PI), mitotic index (MI) and nuclear division index (NDI) were also calculated to determine the cytotoxic/cytostatic effect. Cultures were treated with LOR at three concentrations (5, 15 and 25 µg/ml) for 48 h. Results: Although the MI significantly decreased at the higher concentrations (15 and 25 µg/ml) compared with negative (solvent) control, LOR indicated weaker cytotoxic potential in PI and NDI values at all the tested concentrations. LOR increased the frequencies of SCE, CA and MN in all lymphocyte cultures. However, significant increase was observed in MN at the medium and highest doses (15 and 25 µg/ml) and in CA at the medium dose (15 µg/ml) compared with negative (solvent) control culture. Our results indicate that LOR has cytotoxic and genotoxic effects on human peripheral blood lymphocyte cultures. Discussion: Although most of previously findings have shown that LOR does not reflect genotoxicity, our results indicated that it may be a genotoxic drug. Conclusion: More studies are necessary to elucidate the relationship between cytotoxic, genotoxic and apoptotic effects, and to make a possible risk assessment in patients receiving therapy with this drug.

Therapeutic effect of Azithromycin in the combine-sequential therapy for infants with wheezing

Objective Early studies had confirmed that the combine-sequential therapy in the treatment of acute attacks of wheezing infants was safe and effective, this study aims to further explore the role of oral azithromycin in the combine-sequential therapy. Methods According to the principles of randomized, 56 wheezing infants were divided into Azithromycin group and control group from Aug.2012 to Apr.2013, and there were 29 children in the Azithromycin group and 27 children in the control group.The treatment protocol of Azithromycin group were oral Azithromycin 10 mg/(kg·d), 3 days; oral prednisone 5 mg/d, 3 days; Tulobuterol Patch 0.5 mg/d, 7 days; oral Ioratadine 3 mL/d, 7 days; oral Montelukast 4 mg/d, 7 days.Control group was without Azithromycin, and the rest of drugs were the same as Azithromycin group.The symptom scores of coughing, wheezing, wheezing sound and the difficulty of expectoration in the 1st day, the 3rd day, and the 7th day were recorded. Results 1.The Azithromycin group and the control group could both improve the children's symptom scores of coughing, wheezing, wheezing sound and the difficulty of expectoration, the 2 groups of children before and after treatment of the symptom scores differences were statistically significant (5.41±1.40, 4.85±1.13 vs 1.14±0.78, 2.93±1.00)(S=217.5, 147.0, all P<0.05).2.The Azithromycin group had more improvement at the symptom scores of coughing, wheezing, wheezing sound and the difficulty of expectoration than those of the control group in the third day (0.52±0.51, 0.28±0.45, 0.24±0.44, 0.38±0.49 vs 0.89±0.42, 0.74±0.45, 0.62±0.69, 0.67±0.48)and the 7th day (0.24±0.44, 0.21±0.41, 0.07±0.26, 0.21±0.41 vs 0.52±0.51, 0.48±0.51, 0.37±0.49, 0.48±0.51), and the symptom score differences were statistically significant(Z=2.75, 3.44, 2.90, 2.12, 2.11, 2.13, 2.71, 2.13, all P<0.05). Conclusions Azithromycin + Tulobuterol patch + Prednisone + Loratadine + Montelukast combination consisting of sequential therapy can improve children with acute wheezing cough, wheezing, wheezing, difficulty of the expectoration symptoms, azithromycin is an effective component of infants wheezing combined sequential treatment regimen. Key words: Azithromycin; Wheezing; Combine; Sequential; Infant

A prospective study on inhaled corticosteroids combined with oral montelukast to prevent exacerbation of airway allergic inflammation in children

Objective To investigate the effect on preventing exacerbation of airway allergy inflammation by inhaled corticosteroid with a spacer through nose and mouth combined with oral montelukast,in order to prevent transformation from allergic rhinitis (AR) to cough variant asthma (CVA) and bronchial asthma (BA).Methods 232 cases of AR were randomly divided into control group (114 cases) and observation group (118 cases).Control group was treated by oral loratadine (Wt ＜ 30 kg,5 mg once daily; Wt ≥ 30 kg,10mg once daily).Observation group was administered by inhaled fluticasone propionate with 125 μ g twice daily and oral montelukast (1-5 yrs,4 mg once daily; 6-14 yrs,5 mg once daily) on basis of control group.When patients' symptoms were controlled,dose of fluticasone propionate was reduced to once daily.Fluticasone was inhaled with a spacer,patients were required to close their mouth and to breathe for 1 minute through their nose if they were able to cooperate.Course of treatment was 3 months in both groups.After treatment,patients were followed up at least once a month for 3 years.If patients' symptoms weren' t controlled or didn' t recur,treatment above would be continued for another 3 months.The unhealed and recurrent rates of AR,incidence of CVA and BA were compared between two groups half a year,1 year,2 years and 3years after treatment.If patients were diagnosed with BA,they would be treated by routine therapy of BA.If patients corresponded to diagnostic criteria of CVA.they would be randomly divided into control group and observation group again.Observation group would continue to he treated by above-mentioned therapy for half a year,while control group was treated by antitussives,expectorants and antibiotics.Patients were followed up every 1-2 weeks when their symptoms weren't controlled,then they were followed up once a month when their symptoms were controlled.Follow-up lasted for 3 years.The unhealed and recurrent rates of CVA,incidence of BA were compared between two groups half a year,1 year,2 years and 3 years after treatment.Results Half a year,1 year,2 years and 3 years after treatment,the unhealed and recurrent rates of AR in control group and observation group were 52％,60％,71％,80％ and 14.15％,16.38％,18.87％,25.47％respectively (P ＜ 0.001),the incidences of CVA in control group and observation group were 40％,48％,57％,71％ and 15.09％,16.98％,20.75％,23.73％ respectively (P ＜ 0.001),the incidences of BA in control group and observation group were 30％,39％,47％,53％ and 11.32％,13.21％,16.04％,18.87％ respectively (P ≤ 0.001).In patients with CVA,the unhealed and recurrent rates in control group and observation group were 45％,55％,62.5％,75％ and 17.5％,25％,30％,37.5％ respectively (P ＜ 0.01),incidences of BA in control group and observation group were 35％,45％,60％,70％ and 10％,12.5％,15％,17.5％ respectively (P ＜ 0.01).As the time of follow-up extended,above-mentioned rates in control group had increased more obviously than those in observation group.Conclusions Repetitions of AR and CVA were prevented,and transformation from AR to CVA and BA was also prevented by inhaled corticosteroid combined with oral montelukast,which could stop airway allergy inflammation from worsening. Key words: Inhalant corticosteroid; Montelukast; Airway allergy inflammation; Children

Simultaneous determination of antihistamine anti-allergic drugs, cetirizine, domperidone, chlorphenamine maleate, loratadine, meclizine and buclizine in pharmaceutical formulations, human serum and pharmacokinetics application

This article describes a new, accurate and highly specific high performance liquid chromatographic method with UV detection (HPLC-UV) for the simultaneous determination of cetirizine HCl (CZ), chlorphenamine maleate (CPM), loratadine (LTD), domperidone (DP), buclizine (BZ) and meclizine (MZ) in pharmaceutical dosage form and human serum, involving pyridoxine (PYD) as the internal standard. The mobile phase consists of heptane sulphonic acid salt buffer and acetonitrile, drawn at a flow rate of 1.0 mL min−1 using a symmetry C18 column with UV detection at 230 nm. The intraday and inter-day precision measurements showed coefficients of variation always less than one. The calibration curve was tested in the range of 10–2150 ng mL−1 and the correlation coefficient of >0.9990 in all cases was obtained. The averages of the absolute and relative recoveries were found to be in the range of 98 to 102%. Up to six antihistamines were separated in the same chromatogram with good resolution. The proposed HPLC method has reasonable applications in pharmaceutical tablet dosage form and pharmacokinetics studies.

Tacrolimus ointment for children's atopic dermatitis and its influence on malassezia's colonization

Objectives To evaluate the influence of tacrolimus ointment on malassezia's colonization in the lesional areas of the children with atopic dermatitis (AD).Methods The children with AD were randomly divided into a treatment group and a control group.Both groups orally administered loratadine tablets.In addition,the treatment group were treated with 0.03％ tacrolimus ointment and the control group was given Vitamin E cream twice a day for 3 weeks.The SCORAD integral drop index was used to evaluate the efficacy.Values of SCORAD and malassezia colonization density were compared before,day 7,14,and 21 of,and 14 and 28 days after the treatment.Pearson correlation analysis was used to assess the dependability between malassezia colonization density and the severity of disease.Results The SCORAD value of the treatment group markedly decreased after the treatment.The efficacy rate was 95.65 ％ in treatment group and 66.67 ％ in the control group (P ＜ 0.05).28 days after the treatment,one case recurred and the efficacy rate was 91.30％ in the treatment group and 3 cases recurred and the efficacy rate was 50.00％ in the control group,with significant differences (P ＜ 0.05).There was no significant correlation between malassezia colonization density and SCORAD integral before and after the treatment.Day 7,14,and 21 of the treatment,Malassezia colonization densities were lower in the treatment group than in the control group(P ＜ 0.05).Conclusions 0.03％ tacrolimus ointment for children with AD is effective and safe,has a low recurrence rate,and can reduce the malassezia colonization density on the surface of lesional area. Key words: Atopic dermatitis; Tacrolimus; Malassezia; Colonization

Thin layer chromatography–densitometric determination of some non‐sedating antihistamines in combination with pseudoephedrine or acetaminophen in synthetic mixtures and in pharmaceutical formulations

The combination of certain non-sedating antihistamines (NSA) such as fexofenadine (FXD), ketotifen (KET) and loratadine (LOR) with pseudoephedrine (PSE) or acetaminophen (ACE) is widely used in the treatment of allergic rhinitis, conjunctivitis and chronic urticaria. A rapid, simple, selective and precise densitometric method was developed and validated for simultaneous estimation of six synthetic binary mixtures and their pharmaceutical dosage forms. The method employed thin layer chromatography aluminum plates precoated with silica gel G 60 F254 as the stationary phase. The mobile phases chosen for development gave compact bands for the mixtures FXD-PSE (I), KET-PSE (II), LOR-PSE (III), FXD-ACE (IV), KET-ACE (V) and LOR-ACE (VI) [Retardation factor (Rf ) values were (0.20, 0.32), (0.69, 0.34), (0.79, 0.13), (0.36, 0.70), (0.51, 0.30) and (0.76, 0.26), respectively]. Spectrodensitometric scanning integration was performed at 217, 218, 218, 233, 272 and 251 nm for the mixtures I-VI, respectively. The linear regression data for the calibration plots showed an excellent linear relationship. The method was validated for precision, accuracy, robustness and recovery. Limits of detection and quantitation were calculated. Statistical analysis proved that the method is reproducible and selective for the simultaneous estimation of these binary mixtures.