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

Drug Des Devel Ther. 2019 Oct 18:13:3625-3634. doi: 10.2147/DDDT.S215316. eCollection 2019.

Abstract

Purpose: The aim of this study is to assess the bioequivalence of a new generic formulation and the branded formulation of levocetirizine dihydrochloride in healthy Chinese volunteers under fasting and fed conditions, and food-intake effect on the pharmacokinetic properties is also evaluated.

Patients and methods: Volunteers were randomly allocated into two groups to receive a single oral dose of generic formulation and branded formulation under fasting or fed conditions, respectively. Blood samples were collected at designated time points. Plasma concentrations of levocetirizine were determined by UFLC-MS/MS. Safety evaluations were carried out through the study. The main pharmacokinetic parameters of the two formulations of levocetirizine were calculated using non-compartmental analysis incorporated in WinNonlin® 7.0 software.

Results: Forty-nine volunteers were enrolled; 46 completed the studies. Under fasting and fed conditions, the 90% confidence intervals for the geometric mean of generic/branded ratios were in the range of 94.75-107.24% and 99.98-114.69% for the maximum observed concentration, and 97.13-102.50% and 98.36-103.98% for the area under the concentration-time curve. As a result of food intake before administration, the reduced rate and extent of absorption of levocetirizine were observed. Both formulations were generally well tolerated, with no serious adverse reactions reported.

Conclusion: The two formulations demonstrated essentially identical pharmacokinetic profiles and were all well within the FDA/CFDA bioequivalence standards. Meanwhile, food intake can delay the absorption rate and reduced the bioavailability of levocetirizine in healthy Chinese volunteers.

Keywords: bioequivalence; food effect; healthy Chinese volunteers; levocetirizine; pharmacokinetics.

Publication types

  • Comparative Study
  • Randomized Controlled Trial

MeSH terms

  • Administration, Oral
  • Adolescent
  • Adult
  • Area Under Curve
  • Biological Availability
  • Cetirizine / administration & dosage*
  • Cetirizine / adverse effects
  • Cetirizine / pharmacokinetics
  • Chromatography, High Pressure Liquid
  • Cross-Over Studies
  • Drugs, Generic / administration & dosage*
  • Drugs, Generic / adverse effects
  • Drugs, Generic / pharmacokinetics
  • Female
  • Food-Drug Interactions*
  • Histamine H1 Antagonists, Non-Sedating / administration & dosage*
  • Histamine H1 Antagonists, Non-Sedating / adverse effects
  • Histamine H1 Antagonists, Non-Sedating / pharmacokinetics
  • Humans
  • Male
  • Pilot Projects
  • Tandem Mass Spectrometry
  • Therapeutic Equivalency
  • Young Adult

Substances

  • Drugs, Generic
  • Histamine H1 Antagonists, Non-Sedating
  • levocetirizine
  • Cetirizine

Grants and funding

This study was supported by the Fujian Science and Technology Innovation Joint Project (no. 2017Y9036) and Fujian Health and Family Planning Young and Middle-aged Talents Training Project (no. 2018-ZQN-35).