European Journal of Clinical Pharmacology

, Volume 57, Issue 8, pp 571–582

Absorption, distribution, metabolism and excretion of [14C]levocetirizine, the R enantiomer of cetirizine, in healthy volunteers

  • Margherita Strolin Benedetti
  • Michel Plisnier
  • Jacques Kaise
  • Laura Maier
  • Eugène Baltes
  • Catherine Arendt
  • Nigel McCracken
Pharmacokinetics and Disposition

DOI: 10.1007/s002280100364

Cite this article as:
Strolin Benedetti, M., Plisnier, M., Kaise, J. et al. Eur J Clin Pharmacol (2001) 57: 571. doi:10.1007/s002280100364

Abstract.

The main goal of the present study was to investigate the absorption and disposition of levocetirizine dihydrochloride, the R enantiomer of cetirizine dihydrochloride, following a single oral administration (5 mg) of the 14C-labelled compound in healthy volunteers. Configurational stability was also investigated. Levocetirizine was rapidly and extensively absorbed: 85.4% and 12.9% of the radioactive dose were recovered 168 h post-dose in urine and faeces, respectively. Levocetirizine and/or its metabolites were not, or only very poorly, associated with blood cells, as the blood-to-plasma ratio was 0.51 to 0.68. The mean apparent volume of distribution (Vz/F) was 26.9 l (0.3 l/kg) indicating that the distribution of levocetirizine is restrictive. The protein binding of radiolabelled levocetirizine was 96.1% 1 h after administration. In vitro, at concentrations ranging from 0.2 µg/ml to 1 µg/ml, the protein binding was 94.8% to 95.0%. Levocetirizine is very poorly metabolised. The cumulative 48-h excretion as parent compound accounted for 85.8% of the oral dose, equivalent to 95% of the total radioactivity excreted at this time. At least 13 minor metabolites were detected in urine and represented 2.4% of the dose at 48 h. The metabolic pathways involved in levocetirizine metabolism are oxidation (hydroxylation, O-dealkylation, N-oxidation and N-dealkylation), glucuroconjugation, taurine conjugation and glutathione conjugation with formation of the mercapturic acids. There was no evidence of chiral inversion of levocetirizine in humans. This result is consistent with that obtained in preclinical studies.

Absorption Disposition Enantiomer

Copyright information

© Springer-Verlag 2001

Authors and Affiliations

  • Margherita Strolin Benedetti
    • 1
  • Michel Plisnier
    • 2
  • Jacques Kaise
    • 2
  • Laura Maier
    • 2
  • Eugène Baltes
    • 2
  • Catherine Arendt
    • 2
  • Nigel McCracken
    • 3
  1. 1.UCB Pharma, 21 rue de Neuilly, 92003 Nanterre Cedex, France
  2. 2.UCB Pharma, Chemin du Foriest, 1420 Braine l'Alleud, Belgium
  3. 3.Inveresk Research, Tranent EH33 2NE, Scotland, UK