Separation and identification of cetirizine enantiomers in human urine by capillary electrophoresis and circular dichroism independent of their standards.

Enantioseparation and determination of chiral drugs are of vital importance in biochemical and pharmaceutical research due to the different biological activity, mechanism, and toxicity of individual enantiomers. As a second-generation H(1)-antagonist, cetirizine's pharmaceutical activity is mainly derived from the levocetirizine while the dextro-enantiomer is ineffective and even associated with side effects. Herein, the enantiomers of cetirizine were separated by capillary electrophoresis and identified by electronic circular dichroism. Satisfactory linear relationship was found between the circular dichroism signal at λmax and the electrophoretic peak area difference in the nonracemic mixture of enantiomers. It made possible identification and quantification of cetirizine enantiomers independent of single enantiomer standards. The method's feasibility was demonstrated on the enantiomeric excess experiments of oral drugs measured in human blank urine. Additionally, the separation and determination of cetirizine in human urine after administration were also realized by capillary electrophoresis, indicating the method was sensitive enough for pharmacokinetic study.

Spectroscopic interactions of non-insulin-dependent diabetes mellitus with levocetirizine.

Non insulin dependent diabetes mellitus (NIDDM) drugs such as glibenclamide and metformin is employed to heterogeneous disorder characterized by alteration in production of glucose due to impairment of both insulin secretion and insulin action. These patients might suffer with allergic rhinitis and in this case, there is a possibility to maintain patient on levocetirizine, an anti-allergic drug commonly used in rhinitis. The object of the present study is to detect possible interaction between glibenclamide or metformin with levocetirizine Current study was performed using UV spectroscopic technique sing simultaneous equation in pH simulated to gastric juice (pH 1), pH 4, pH 7.4 and in pH 9. All drugs followed Beer Lambert's Law. Results showed that glibenclamide and metformin can increase or decrease availability of levocetirizine and in the same way levocetirizine can alter availabilities of glibenclamide and metformin in different pH. Hence, drug interaction between glibenclamide or metformin with levocetirizne occurred. This may be due to his may be due to the charge transfer or binding capabilities of these drugs which resulted in significantly changed availability of NIDDIM as well as levocetirizine. Therefore, co-administration of these drugs should be avoided and furtherinvestigations at clinical and pre-clinical levels should be done.

Spectroscopic interaction studies of H2 receptor antagonists with levocetirizine.

Patients with allergic rhinitis may also suffer abdominal pain, gastritis or peptic ulcer. In this condition patient may use levocetirizine with famotidine or ranitidine. These drugs have potential to interact with another drug and form complex. The aim of the present study is to evaluate the possible drug drug interaction with each other which may cause increase or decrease of therapeutic effects. For this purpose, validity of Beer Lambert law was checked, lone availability of famotidine (20gm), ranitidine (150gm) and levocetirizine (5mg) were studied in pH simulated to gastric juice (pH 1), pH 4, pH 7.4 and in pH 9 and finally percent availabilities of these drugs were calculated with the help of simultaneous equation. Results showed high percentage of levocetirizine in all pH as 300.32%, 514.41%, 173.38% and 220.68% in presence of famotidine but very low availability of famotidine as 5.36%, 35.38%, 51.87% and 10.89% in presence of levocetirizine. In the case of levocetirizine and ranitidine interaction, zero percent levocetirizine was available at pH 1and 9, 56.28% in pH 4 and 191.1% in pH 7.4. On the other hand, ranitidine was available as 95.36%, 127.93%, 41.47% and 144.3%. These results showed that percentage of all drugs were altered in presence of each other due to drug-drug interaction. This may be due to the charge transfer binding capabilities of the drugs which resulted in significantly changed availability of famotidine, ranitidine as well as levocetirizine.

Comparative pharmacokinetics of a montelukast/levocetirizine fixed-dose combination chewable tablet versus individual administration of montelukast and levocetirizine after a single oral administration in healthy Korean male subjects
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OBJECTIVE: Asthma patients often have co-existing symptoms of allergic rhinitis and are often prescribed with both asthma and rhinitis treatments such as montelukast and levocetirizine. The objective of this study was to compare the pharmacokinetic profiles of a montelukast/levocetirizine fixed-dose combination chewable tablet with individual administration of montelukast and levocetirizine in healthy subjects. MATERIALS AND METHODS: A randomized, open-label, single-dose crossover study was conducted in healthy male subjects. One of the following treatments was administered in each period: co-administration of 1 chewable tablet of montelukast 5 mg and 1 tablet of levocetirizine 5 mg or administration of 1 chewable tablet of montelukast/levocetirizine 5/5 mg fixed-dose combination. Serial blood samples were collected up to 48 hours post dose. Plasma drug concentrations were measured by liquid chromatography/tandem mass spectrometry. Pharmacokinetic parameters, including maximum plasma concentration (Cmax) and area under the plasma concentration versus time curve from dosing to the last measurable concentration (AUClast), were determined by non-compartmental analysis. The geometric least-square mean (GLSM) ratios and associated 90% confidence intervals (CIs) of Cmax and AUClast were calculated to evaluate pharmacokinetic equivalence. RESULTS: A total of 22 subjects were included in pharmacokinetic analysis. The GLSM ratios and 90% CIs of Cmax and AUClast were 1.0054 (0.9535 - 1.0601) and 1.0628 (1.0013 - 1.1281) for montelukast and 1.0105 (0.9488 - 1.0764) and 1.0396 (0.9935 - 1.0879) for levocetirizine, respectively. CONCLUSION: The pharmacokinetic parameters of montelukast and levocetirizine when administered as separate tablets or as a fixed-dose combination were compared, and the parameters met the pharmacokinetic equivalence criteria. (ClinicalTrials.gov Identifier: NCT03371849).

Development of medicated chewing gum of taste masked levocetirizine dihydrochloride using different gum bases: in vitro and in vivo evaluation.

Objective: The aim of this study was to develop medicated chewing gum (MCG) formulation for taste-masked levocetirizine dihydrochloride (LCZ) that can provide fast drug release into the salivary fluid.Methods: Taste-masked LCZ was first prepared by two methods: cyclodextrin complexation using Kleptose or Captisol and formation of drug resin complex using Kyron T-154 or Kyron T-314 to overcome poor LCZ palatability. MCGs were then prepared using the taste-masked drug, gum base (Artica-T, Chicle, or Health In Gum (HIG), plasticizer (glycerol or soy lecithin at 6 or 8% of the final gum weight). The developed MCGs were evaluated for physical properties, content uniformity, and drug release. Best release MCGs were evaluated thermally to investigate the plasticizer effectiveness and for ex vivo chew out study to confirm adequate drug release. Drug bioavailability was determined for selected formula compared to commercial tablets.Results: Based on taste-masking efficiency, drug/Kleptose complex (1:3 molar ratio) was chosen for incorporation into chewing gums. Physical properties and drug release showed that gum base type, plasticizer type, and level affected not only physical properties but also drug release from MCGs. Thermal study showed decreased glass transition temperature (Tg) with increased plasticizer level. Chew out study confirmed almost complete drug release after a few minutes of chewing. Pharmacokinetic results showed shorter tmax (0.585 vs. 1.375 h) and higher Cmax (0.113 vs. 0.0765 µg/mL) for MCGs than conventional tablets.Conclusion: Results provided evidence that MCGs could be a better alternative to conventional tablet formulations with improved bioavailability and enhanced palatability.

Development of nanoemulsion gel drug delivery systems of cetirizine; factorial optimisation of composition, in vitro evaluation and clinical study.

Aim: This work aimed to develop topical nanoemulsion gels of cetirizine, a second-generation antihistamine, to avoid its oral intake drawbacks and enhance skin permeation.Methods: Cetirizine nanoemulsions were formulated and characterised for their particle size, polydispersity index, zeta potential, drug release and drug permeation through rat skin. The optimised formulation, obtained using 23 full factorial design, was incorporated in carbopol and chitosan gels and evaluated clinically for urticaria treatment.Results: The optimised formulation had particle size of 32.015 ± 1.87 nm, polydispersity index of 0.29 ± 0.04, zeta potential of -19.31 ± 0.43 mV, cetirizine percent released of 98.50 ± 1.23% and permeability coefficient of 7.65 cm.h-1. Cetirizine nanoemulsion gels were more effective than their control gels in urticaria treatment with significant decrease in the degree of wheals and itching and higher recovery percent.Conclusion: Cetirizine nanoemulsion topical gels are expected to be a rational and effective tool for avoiding cetirizine oral side effects and targeting the affected skin.

Simultaneous bioanalysis and pharmacokinetic interaction study of acebrophylline, levocetirizine and pranlukast in Sprague-Dawley rats.

The combination of acebrophylline (ABP), levocetirizine (LCZ) and pranlukast (PRN) is used to treat allergic rhinitis, asthma, hay-fever and other conditions where patients experience difficulty in breathing. This study was carried out with the aim of developing and validating a reverse-phase high-performance liquid chromatographic bioanalytical method to simultaneously quantitate ABP, LCZ and PRN in rat plasma. The objective also includes determination of the pharmacokinetic interaction of these three drugs after administration via the oral route after individual and combination treatment in rat. Optimum resolution between the analytes was observed with a C18 Kinetex column (250 mm × 4.6 mm × 5 µm). The chromatography was performed in a gradient elution mode with a 1 mL/min flow rate. The calibration curves were linear over the concentration range of 100-1600 ng/mL. The intra- and inter-day precision and accuracy were found to be within acceptable limits as specified in US Food and Drug Administration guideline for bioanalytical method validation. The analytes were stable on the bench-top (8 h), after three freeze-thaw cycles, in the autosampler (8 h) and as a dry extract (-80°C for 48 h). The statistical results of the pharmacokinetic study in Sprague-Dawley rats showed a significant change in pharmacokinetic parameters for PRN upon co-administration of the three drugs.

Tamanu oil potentiated novel sericin emulgel of levocetirizine: repurposing for topical delivery against DNCB-induced atopic dermatitis, QbD based development and in vivo evaluation.

The present study was aimed at preparing and evaluating levocetirizine (LCZD) loaded emulgel containing tamanu oil and sericin for atopic dermatitis (AD) therapy. The emulgel envisaged topical delivery of LCZD utilising natural antioxidants for superior therapeutic outcomes when compared with other conventional therapy. Tamanu oil based microemulsion (ME) was optimised utilising Box-Behnken design (BBD). The OPT-ME displayed globule size 379.5 ± 2.33 nm, polydispersity index 0.284, drug loading 0.41 ± 0.01% w/w, entrapment efficiency 94.34 ± 2.11% w/w and drug release 86.24 ± 4.90% respectively over a period of 24 h. The optimised formulation (OPT-ME) was further incorporated into sericin gel to form emulgel (LSE). In vivo pharmacodynamic studies revealed enhanced therapeutic potential of emulgel in terms of reduced scratching frequency and erythema score when compared with conventional gel. The superior therapeutic potential was further witnessed through histopathological and biochemical studies. The emulgel can be an alternative appropriate dosage form for the treatment of AD.

Pharmacokinetics of hydroxyzine and cetirizine following oral administration of hydroxyzine to exercised Thoroughbred horses.

Hydroxyzine is a first-generation antihistamine and cetirizine, a second-generation antihistamine and active metabolite of hydroxyzine. Hydroxyzine is commonly used in performance horses and as such its use in closely regulated; however, there are no published studies suitable for establishing appropriate regulatory recommendations. In the current study, 12 exercised Thoroughbred research horses received a single oral administration of 500 mg of hydroxyzine. Blood and urine samples were collected prior to and up to 96 hr postdrug administration and concentrations of hydroxyzine and cetirizine determined using liquid chromatography-tandem mass spectrometry. A joint parent/metabolite population 2-compartment pharmacokinetic model with first-order absorption and elimination was utilized to describe the pharmacokinetics of both compounds. Serum hydroxyzine and cetirizine concentrations were above the limit of quantitation (0.1 ng/ml) of the assay at 96 hr (the last time point sampled). The terminal half-life was 7.41 and 7.13 hr for hydroxyzine and cetirizine, respectively. Findings from this study suggest that a prolonged withdrawal time should be observed if this compound is used in performance administered to performance horses and is classified as prohibited substance by the applicable regulatory body.

Comparison of the pharmacokinetics and tolerability of montelukast/levocetirizine administered as a fixed-dose combination and as separate tablets.

OBJECTIVE: A novel fixed-dose combination (FDC) capsule of 10/5 mg of montelukast/levocetirizine may lead to better compliance than two separate tablets taken together. The aim of this study was to evaluate the pharmacokinetics (PK) and tolerability of an FDC of montelukast and levocetirizine compared to separate tablets. MATERIALS AND METHODS: A randomized, open-label, single-dose, two-sequence, two-period, crossover study was conducted with healthy male subjects. In each period, either an FDC or separate tablets were administered orally, and serial blood samples were collected for PK analysis for up to 34 hours after dosing. PK parameters were calculated using noncompartmental methods. The 90% confidence intervals (CIs) of the geometric mean ratios (GMRs) of the maximum plasma concentration (Cmax) and the area under the curve to the last measurable concentration (AUClast) for the two interventions were estimated. Tolerability assessments were performed for all the subjects who received the drug at least once. RESULTS: The PK profiles of the two interventions were comparable. For montelukast, the GMRs and 90% CIs for the Cmax and AUClast were 0.9800 (0.8903 - 1.0787) and 1.0706 (0.9968 - 1.1498), respectively. The corresponding values for levocetirizine were 0.9195 (0.8660 - 0.9763) and 1.0375 (1.0123 - 1.0634), respectively. Both interventions were well tolerated. CONCLUSION: The PK and tolerability profiles of montelukast and levocetirizine after a single oral administration were comparable between the FDC and separate tablets. For patients with allergic rhinitis who require a combination treatment, the FDC of montelukast and levocetirizine will be a convenient therapeutic option.
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Pediatric Dispersible Tablets: a Modular Approach for Rapid Prototyping.

PURPOSE: The design of pediatric formulations is challenging. Solid dosage forms for children have to meet the needs of different ages, e.g. high number of dosing increments and strengths. A modular formulation strategy offering the possibility of rapid prototyping was applied. Different tablet compositions and the resulting tablet characteristics were investigated for dispersible tablets using customized analytical methods. METHODS: Fluid bed granules were blended with extragranular components, and compressed to tablets. Disintegration behavior was studied with a Texture Analyzer and a Tensiometer. RESULTS: Methods for determination of disintegration time and water uptake of tablets were developed with a Texture Analyzer, and a Tensiometer, respectively. Twenty-two different tablet formulations were prepared and analyzed with respect to disintegration time, hardness, friability, and viscosity. Multivariate data analysis revealed a high impact of type and amount of viscosity enhancer on the disintegration behavior of tablets. An optimized formulation was selected with a disintegration time of 24 s. CONCLUSION: Methods providing additional information on the disintegration behavior of dispersible tablets compared to standard pharmacopoeia methods were established. Selecting the right type and level of viscosity enhancer and superdisintegrant was critical for developing pediatric tablets with a disintegration time of less than 30 s but still pleasant mouth feel.

Elimination of cetirizine following administration of multiple doses to exercised thoroughbred horses.

Cetirizine is an antihistamine used in performance horses for the treatment of hypersensitivity reactions and as such a withdrawal time is necessary prior to competition. The objective of the current study was to describe the disposition and elimination of cetirizine following oral administration in order to provide additional serum concentration data upon which appropriate regulatory recommendations can be established. Nine exercised thoroughbred horses were administered 0.4 mg/kg of cetirizine orally BID for a total of five doses. Blood samples were collected immediately prior to drug administration and at various times postadministration. Serum cetirizine concentrations were determined and selected pharmacokinetic parameters determined. The serum elimination half-life was 5.83 ± 0.841 h. Average serum cetirizine concentrations were still above the LOQ of the assay (0.05 ng/mL) at 48 h (final sample collected) postadministration of the final dose.

Ethosomes-based topical delivery system of antihistaminic drug for treatment of skin allergies.

Cetirizine is indicated for the treatment of allergic conditions such as insect bites and stings, atopic and contact dermatitis, eczema, urticaria. This investigation deals with development of a novel ethosome-based topical formulation of cetirizine dihydrochloride for effective delivery. The optimised formulation consisting of drug, phospholipon 90 G™ and ethanol was characterised for drug content, entrapment efficiency, pH, vesicular size, spreadability and rheological behaviour. The ex vivo permeation studies through mice skin showed highest permeation flux (16.300 ± 0.300 µg/h/cm(2)) and skin retention (20.686 ± 0.517 µg/cm(2)) for cetirizine-loaded ethosomal vesicles as compared to conventional formulations. The in vivo pharmacodynamic evaluation of optimised formulation was assessed against oxazolone-induced atopic dermatitis (AD) in mice. The parameters evaluated were reduction in scratching score, erythema score, skin hyperplasia and dermal eosinophil count. Our results suggest that ethosomes are effective carriers for dermal delivery of antihistaminic drug, cetirizine, for the treatment of AD.

Engineering of electrospun polycaprolactone/polyvinyl alcohol-collagen based 3D nano scaffolds and their drug release kinetics using cetirizine as a model drug.

Combining the versatility of electrospinning with the biocompatibility of Polycaprolactone and Collagen, this study aims to create advanced 3D nano scaffolds for effective drug delivery. Ceramic materials like hydroxyapatite (nHAp) are incorporated as bioactive agents in the fibers. Electrospun PCL (Polycaprolactone)/collagen nanofibers and PVA (Poly-vinyl alcohol)/collagen are promising tissue-engineering substitutes with high biocompatibility, low cytotoxicity, and great tensile strength. Small pores in these nanofibers play a major role in drug delivery system. Owing to its short half-life, limited solubility, restricted bioavailability as well as re-crystallization concerns, the application of Cetirizine (CIT) has found little relevance. Electrospun nanofibers impregnated with CIT provide an excellent solution to combat these limitations, yield sustained drug release along with hampering drug re-crystallization. CIT-loaded polyvinyl alcohol (PVA)/collagen (Col) and CIT-loaded PVA/Col/nHAp nanofibers were characterized and further CIT anti-crystallization as well as release behaviors were investigated. FESEM and HRTEM were used to observe the morphology of the as-synthesized nanofibers. FTIR spectroscopy, water contact angle measurement and drug release studies verified the differences in performance of CIT-loaded PVA/Col and PVA/Col/nHAp nanofibers. The release trend of CIT through these as-synthesized nanoscaffolds was analyzed by various kinetic models and exhibited sustained release of CIT for up to 96 h.

H(1)-antihistamines and urticaria: how can we predict the best drug for our patient?

Urticaria, and especially chronic spontaneous urticaria (CSU), is a difficult condition to treat. Consequently, clinicians need to use the best H(1)-antihistamines currently available and the pharmaceutical industries need to keep developing H(1)-antihistamines that are more effective than the ones we have today. To do this we need to be able to compare the clinical efficacy of both established and new drugs. Obviously, the ideal way to do this is to use head-to-head studies in CSU. However, such studies are extremely expensive and, in the case of novel molecules, have ethical and logistical problems. Consequently, we need to have predictive models. Although determination of Ki, an indicator of the in vitro potency of an H(1)-antihistamine, may help in the initial selection of candidate molecules, the large differences in volume of distribution and tissue accumulation in humans, precludes this from being a good predictor of clinical efficacy in CSU. From the data reviewed in this article, especially the direct comparative data of desloratadine and levocetirizine in weal and flare studies and CSU, weal and flare response would appear to be the best indicator we have of effectiveness of H(1)-antihistamines in clinical practice. However, it must be pointed out that the conclusion is, essentially, based on detailed comparisons of two drugs in studies sponsored by pharmaceutical companies. Consequently, to confirm the conclusions of this review, a multicentre study independent from the influence of pharmaceutical companies should be commissioned to compare the speed of onset and effectiveness of desloratadine, fexofenadine and levocetirizine in chronic spontaneous urticaria and against histamine-induced weal and flare responses in the same patients so that we have a clear understanding of the predictive value of our models.

Simultaneous determination of levocetirizine and pseudoephedrine in dog plasma by liquid chromatography-mass spectrometry in the presence of dextrocetirizine.

PURPOSE: This study describes the development of a rapid and sensitive LC-ESI-MS assay for simultaneous enantioselective determination of levocetirizine and pseudoephedrine in dog plasma in the presence of dextrocetirizine. METHODS: Separations were achieved on an Ultron ES-OVM chiral column using the mobile phase consisting of 10 mM aqueous NH4OAc (pH 6.6) and acetonitrile (9:1 v/v). RESULTS: The retention times of pseudoephedrine, dextrocetirizine, levocetirizine and diazepam (internal standard) were 5.2, 8.3, 9.6 and 11.6 min, respectively, and the total run time was less than 15 min. The assay was validated to demonstrate the linearity, accuracy and precision, recovery and stability. The calibration curves were linear over the concentration range from 1 - 200 ng/mL for levocetirizine and from 5 - 1000 ng/mL for pseudoephedrine. CONCLUSIONS: The developed assay was successfully applied to a pharmacokinetic study after oral administration of the racemic cetirizine (0.5 mg/kg, or 0.25 mg/kg as levocetirizine) and pseudoephedrine (12 mg/kg) in the dog. This article is open to POST-PUBLICATION REVIEW. Registered readers (see "For Readers") may comment by clicking on ABSTRACT on the issue's contents page.

The impact of P-glycoprotein mediated efflux on absorption of 11 sedating and less-sedating antihistamines using Caco-2 monolayers.

Caco-2 cells were used to compare P-gp mediated efflux and passive permeability using bidirectional transport of 11 antihistamines. An efflux ratio >2 indicated active efflux, with PSC833 and GF120918 used as functional P-gp inhibitors. Antihistamines were measured directly by HPLC or LC/MS. Fexofenadine had an efflux ratio of 37, yet had negligible passive permeability, even in the presence of a pH gradient (0.1 × 10(-6) cm/sec). Its precursor, terfenadine, had an efflux ratio of 2.5, while cetirizine, desloratadine and hydroxyzine were 4, 7 and 14, respectively. After incubation with P-gp inhibitors, these ratios dropped significantly. Loratadine, by contrast, had equivalent transport in both directions and passive permeability was high (24 × 10(-6) cm/sec). Dimenhydrinate was the only other sedating antihistamine to exhibit efflux, with a ratio of 10. Gradient conditions of pH (6/7.4) increased efflux of terfenadine and desloratadine to over 31 and 38 fold respectively, yet this increased efflux was not associated with P-gp. Altering functional P-gp in the gut is likely to influence absorption of some sedating antihistamines such as dimenhydrinate and hydroxyzine and most less-sedating antihistamines except loratadine. In addition, desloratadine exhibits pH dependent efflux which could further induce variable absorption of this antihistamine.

Comparative inhibition by bilastine and cetirizine of histamine-induced wheal and flare responses in humans.

OBJECTIVE AND DESIGN: Comparison of bilastine and cetirizine in inhibiting skin wheal and flare responses over 24 h. SUBJECTS: Twenty-one healthy male volunteers (aged 19-44 years). TREATMENT AND METHODS: Volunteers were randomised to receive single oral doses of 20 or 50 mg bilastine, 10 mg cetirizine or placebo before provocation of wheal and flare responses to 100 mg/ml histamine by skin prick 1.5, 4, 8, 12 and 24 h later. RESULTS: There were no significant differences between overall inhibitions of wheal or flare by 20 mg bilastine and 10 mg cetirizine. Bilastine was faster in onset than cetirizine, inhibitions of wheal and flare at 1.5 h being 89 ± 3 versus 44 ± 14% (P = 0.011) and 85 ± 4 versus 45 ± 14% (P = 0.016), respectively (Student's t test). At 1.5 h, both wheals and flares were inhibited by >70% in 11/12 volunteers taking bilastine and 3/11 taking cetirizine (P = 0.003, Fisher's exact test). There were no significant differences between the drugs at later times. Bilastine 50 mg had a longer duration of action than bilastine 20 mg. CONCLUSIONS: Both 20 mg bilastine and 10 mg cetirizine are effective and of long duration in reducing histamine-induced wheal and flare responses, the major difference between the two drugs being the more rapid onset of action of bilastine.

Levocetirizine Oral Disintegrating Tablet: A Randomized Open-Label Crossover Bioequivalence Study in Healthy Japanese Volunteers.

Levocetirizine is classified as a second-generation antihistamine. Levocetirizine is available for the treatment of allergic disorders such as allergic rhinitis and chronic idiopathic urticaria. This was a single-center, single-dose, open-label, randomized, 2-way crossover study in healthy Japanese male subjects consisting of 2 parts. Part 1 compared the bioavailability of levocetirizine oral disintegrating tablet (ODT) and levocetirizine immediate-release tablet (IRT) taken with water in the fasted state in 24 subjects; all subjects completed this part of the trial. In part 2, the bioavailability of levocetirizine ODT without water was compared with that of levocetirizine IRT with water in the fasted state in 48 subjects; 47 subjects completed this part of the trial. Bioequivalence was demonstrated between levocetirizine IRT 5 mg and ODT 5 mg. The safety profiles were generally similar between levocetirizine ODT and levocetirizine IRT, with no serious adverse events, deaths, or adverse events leading to withdrawal reported during the study.

Cetirizine Reduces Gabapentin Plasma Concentrations and Effect: Role of Renal Drug Transporters for Organic Cations.

Gabapentin (GBP) is an organic cation mainly eliminated unchanged in urine, and active drug secretion has been suggested to contribute to its renal excretion. Our objective was to evaluate the potential drug-drug interaction between GBP and cetirizine (CTZ), an inhibitor of transporters for organic cations. An open-label, 2-period, crossover, nonrandomized clinical trial was conducted in patients with neuropathic pain to evaluate the effect of CTZ on GBP pharmacokinetics. Twelve participants were treated with a single dose of 300 mg GBP (treatment A) or with 20 mg/d of CTZ for 5 days and 300 mg GBP on the last day of CTZ treatment (treatment B). Blood sampling and pain intensity evaluation were performed up to 36 hours after GBP administration. The interaction of GBP and CTZ with transporters for organic cations was studied in human embryonic kidney (HEK) cells expressing the organic cation transporters (OCTs), multidrug and toxin extrusion proteins (MATEs), and OCTN1. CTZ treatment resulted in reduced area under the concentration-time curve and peak concentration compared with treatment A. In treatment B, the lower plasma concentrations of GBP resulted in reduced pain attenuation. GBP renal clearance was similar between treatments. GBP has low apparent affinity for OCT2 (concentration of an inhibitor where the response [or binding] is reduced by half [IC50 ] 237 µmol/L) and a high apparent affinity for hMATE1 (IC50 1.1 nmol/L), hMATE2-K (IC50 39 nmol/L), and hOCTN1 (IC50 2.1 nmol/L) in HEK cells. At therapeutic concentrations, CTZ interacts with hMATE1 and OCTN1. In summary, CTZ reduced the systemic exposure to GBP and its effect on neuropathic pain attenuation. However, CTZ × GBP interaction is not mediated by the renal transporters.