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

Abstract

Objective:

Levocetirizine, 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.

Methods:

The 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 (C_max) and the area under the plasma concentration-time curve from dosing until 48 h post-dose (AUC_0–48) after each treatment.

Clinical Trial registration number:

ClinicalTrials.gov identifier is NCT01622283

Results:

The mean C_max and AUC_0–48 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 C_max and AUC_0–48 were 1.027 (0.968–1.091) and 1.059 (1.024–1.094), respectively.

Limitation:

The 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.

Conclusions:

Levocetirizine 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.

Keywords::

• Levocetirizine
• Cetirizine
• Pharmacokinetics
• Japanese

Transparency

Declaration of funding

This study and its publication were funded by GlaxoSmithKline K.K.

Declaration of financial/other relationships

Hiroko Ino, Katsutoshi Hara, Gosuke Honma, and Yohei Doi are employees of GlaxoSmithKline K.K. Hiroyuki Fukase is employed by CPC Clinical Trial Hospital, Medipolis Medical Research Institute, a company that received funding from GlaxoSmithKline to conduct this study. He has received no direct payment for writing or publishing the manuscript.

Acknowledgments

The authors thank study volunteers for their participation and the staff at CPC Clinical Trial Hospital, Medipolis Medical Research Institute, Kagoshima, Japan for support in conducting the study. They also thank Toshiyasu Hirama for his input in the design, conduct, and interpretation of the study, Akira Wakamatsu for writing assistance and Mika Nakashima for editorial assistance.