Comparison of levocetirizine pharmacokinetics after single doses of levocetirizine oral solution and cetirizine dry syrup in healthy Japanese male subjects

Abstract

ObjectiveLevocetirizine, the R-enantiomer of cetirizine, is classified as a second generation antihistamine used for the treatment of allergic disorders. This study aimed to compare exposure to levocetirizine when given as levocetirizine oral solution (OS) 5 mg to that when given as cetirizine dry syrup (DS) 10 mg, which contains equal proportions of levocetirizine and dextrocetirizine, in healthy Japanese male subjects.MethodsThe study was conducted in an open-label, single dose, randomized and two-way cross-over design. Eligible subjects were allocated to one of two groups and received either levocetirizine OS 5 mg or cetirizine DS 10 mg under fasting conditions, and the alternate treatment after a 7-days washout period. Serial blood samples were taken after each administration, and plasma levocetirizine concentrations were determined using a validated LC-MS/MS method. Pharmacokinetic parameters were calculated by using non-compartmental analysis. Comparisons of levocetirizine pharmacokinetics were conducted with maximum concentration (Cmax) and the area under the plasma concentration-time curve from dosing until 48 h post-dose (AUC0–48) after each treatment.Clinical Trial registration numberClinicalTrials.gov identifier is NCT01622283ResultsThe mean Cmax and AUC0–48 of levocetirizine after a single dose of levocetirizine OS 5 mg and cetirizine DS 10 mg were 203.3 ± 42.49 ng/mL and 1814.9 ± 304.22 ng.hr/mL, and 196.5 ± 31.31 ng/mL and 1710.5 ± 263.31 ng hr/mL, respectively. The ratios and the 90% CIs of the geometric least squares means ratios of Cmax and AUC0–48 were 1.027 (0.968–1.091) and 1.059 (1.024–1.094), respectively.LimitationThe small sample size and single dose design of this study prevent definitive conclusions regarding the pharmacokinetics and safety of levocetirizine OS in a Japanese patient population being made. Study limitations include conducting the study in adult males, not in children.ConclusionsLevocetirizine exposure in plasma was equivalent when given as levocetirizine OS 5 mg and as cetirizine DS 10 mg. Both preparations were safe and well-tolerated in healthy Japanese male subjects.

<p>The Effect Of Food On The Pharmacokinetic Properties And Bioequivalence Of Two Formulations Of Levocetirizine Dihydrochloride In Healthy Chinese Volunteers</p>

“…Pharmacokinetic parameters of levocetirizine measured under a fasting condition in the present study were in agreement with the previous studies 2,15. However, most of the published literature is focused on the bioequivalence of branded-to-generic or generic-to-generic substitutions under the fasting condition.…”

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

“…The sample size calculation was based on the within‐subject estimates of variability (CVw%). CVw% values of approximately 6% and 11% for AUC 0‐48 and C max had been observed, respectively, in a previous study of healthy Japanese male subjects 9 . Based on the conservative assumption for CVw% of 22% (double 11%), it was estimated that a sample size of 23 subjects provided a power of at least 90% to demonstrate bioequivalence in each part.…”

“…CVw% values of approximately 6% and 11% for AUC 0-48 and C max had been observed, respectively, in a previous study of healthy Japanese male subjects. 9 Based on the conservative assumption for CVw% of 22% (double 11%), it was estimated that a sample size of 23 subjects provided a power of at least 90% to demonstrate bioequivalence in each part. After consideration of the treatment assignment, a total of 24 healthy Japanese male subjects were enrolled in each part of the study.…”

Usability of theophylline extended-release dry syrups

“…1 Recently, many drugs have been prepared as dry syrups because they are easy to consume. [2][3][4][5][6] Theophylline extended-release dry syrups are frequently used for the treatment of asthma and asthmatic bronchitis in the clinical setting. 7 In addition to the dry syrup formulation Theo-Dur V R , 7 several generic formulations are also commercially available.…”