Absorption and disposition of levocetirizine, the eutomer of cetirizine, administered alone or as cetirizine to healthy volunteers

The primary objective of the present study was to compare the absorption an d disposition of levocetirizine, the eutomer of cetirizine. when administer ed alone (10 mg) or in presence of the distomer. An additional objective wa s also to investigate the configurational stability of levocetirizine in vi vo in humans. The study was performed in a randomized, two-way cross-over, single-dose design with a wash-out phase of 7 days between the two periods. A total of 12 healthy male and 12 healthy female volunteers were included in the study. Bioequivalence can be concluded from the analysis of the phar macokinetic parameters of levocetirizine when administered alone or as the racemate cetirizine. No chiral inversion occurs in humans when levocetirizi ne is administered, i.e. there is no formation of the distomer. When compar ing the pharmacokinetic characteristics of levocetirizine and the distomer, the apparent volume of distribution of the eutomer is significantly smalle r than that of the distomer (0.41 and 0.60 L/kg, respectively). For an H-1- antagonist a small distribution volume can be considered as a positive aspe ct, both in terms of efficacy and safety. Moreover the non-renal clearance of levocetirizine is also significantly lower than that of the distomer (9. 70 and 28.70 mL/min, respectively), which constitutes an additional positiv e aspect particularly as far as metabolism-based drug interactions are conc erned. The information collected in the present study on the pharmacokineti cs of levocetirizine and the distomer provide additional reasons for elimin ating the distomer and developing levocetirizine as an improvement on cetir izine.