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

Abstract

The primary objective of the present study was to compare the absorption and disposition of levocetirizine, the eutomer of cetirizine, when administered alone (10 mg) or in presence of the distomer. An additional objective was also to investigate the configurational stability of levocetirizine in vivo 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 pharmacokinetic parameters of levocetirizine when administered alone or as the racemate cetirizine. No chiral inversion occurs in humans when levocetirizine is administered, i.e. there is no formation of the distomer. When comparing the pharmacokinetic characteristics of levocetirizine and the distomer, the apparent volume of distribution of the eutomer is significantly smaller than that of the distomer (0.41 and 0.60 L/kg, respectively). For an H1-antagonist a small distribution volume can be considered as a positive aspect, 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 positive aspect particularly as far as metabolism-based drug interactions are concerned. The information collected in the present study on the pharmacokinetics of levocetirizine and the distomer provide additional reasons for eliminating the distomer and developing levocetirizine as an improvement on cetirizine.

Histamina, receptores de histamina e anti-histamínicos: novos conceitos

“…15 Levocetirizine is the active R-enantiomer of racemic cetirizine that obviously does not undergo hepatic metabolization, does not have adverse cardiac effects or drug interactions documented. 41 Levocetirizine is a weak gP substrate; hence, its interaction with other drugs is unlikely in this transporting system. 23 In studies with children from 6 to 12 years old with allergic rhinitis in which levocetirizine was administered for four weeks at a dosage of 5mg/day (adult dosage), the drug showed a minimum incidence of adverse effects, compared to those of placebo.…”

Twenty‐four‐hour activity and consistency of activity of levocetirizine and desloratadine in the skin

“…In the nose, the median histamine nasal threshold concentration quadruples after a single administration of levocetirizine (5 mg), as with cetirizine, whereas activity of the S-isomer is similar to that of placebo [3]; median nasal pressure and sneezing are also significantly reduced by levocetirizine and cetirizine, but not by the S-isomer. The antihistaminic effect of levocetirizine lasts for 24 h. In addition, it is as rapidly absorbed and active as cetirizine, its distomer, according to the bioequivalence analysis of the pharmacokinetic parameters [4]. In our study, levocetirizine was used at 5 mg.…”

Chiral Switch Drugs for Asthma and Allergies: True Benefit or Marketing Hype

“…31 Administration of levocetirizine in healthy volunteers does not result in conversion to the racemate for at least 24 hours after a single dose. 31,32 There are no differences in the pharmacokinetics between cetirizine and levocetirizine and both have a similar volume of distribution suggesting similar penetration through the blood-brain barrier. 32 Levocetirizine and cetirizine are largely excreted in the urine (70%-85% recovery) with no significant hepatic metabolism.…”

“…31,32 There are no differences in the pharmacokinetics between cetirizine and levocetirizine and both have a similar volume of distribution suggesting similar penetration through the blood-brain barrier. 32 Levocetirizine and cetirizine are largely excreted in the urine (70%-85% recovery) with no significant hepatic metabolism. 33 Renal tubular secretion of dextrocetirizine is 40% greater than levocetirizine, but renal tubular secretion accounts for less than 30% of the total renal clearance, and thus, there is no expected interaction between the enantiomers.…”