RATIONALE: Medication concentrations at receptor sites can be approximated by free plasma concentrations (fraction not bound to plasma proteins), and are useful in describing the pharmacodynamic response to medications. We hypothesized that the H1-receptor occupancy of levocetirizine (L) in children receiving L 5 mg would be similar to the L H1-receptor occupancy in adults receiving the same dose (Inflamm Res 2005;54 in press).
METHODS: In children, plasma L concentrations (PLC) and percent suppression of the wheal (W) and flare (F) responses induced by epicutaneous histamine 1 mg/mL were determined pre-dose, and at frequent, pre-defined intervals for more than 24 h after a single L 5 mg oral dose. (J Allergy Clin Immunol 2005;116:355-61). In the present study, L H1-receptor occupancies were calculated using free PLC (free = 8.79% total PLC; Fund Clin Pharmacol 2004;18:399-411) and L binding constants (koff/kon = Ki = 3 nM; Mol Pharmacol 2002;61:391-9).
RESULTS: In 14 children, mean (±SEM) age 8.6±0.4 years, free PLC was 50±4 nM at 4 h and 5±1 nM at 24 h, compared to 28 nM and 4 nM in adults. At 4 h, W/F suppression was 100%/94±2% (children) and 100%/89% (adults). At 24 h, W/F suppression was 72±6%/90±3% (children) and 60%/74% (adults). In the children, L H1-receptor occupancies at 4 h and 24 h were 94±0.4% and 60±3%, compared to 90% and 57% respectively in adults.
CONCLUSIONS: The H1-receptor occupancy data support once daily L dosing in children age 6-11 years, as is recommended for adults.
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Funding: UCB S.A.
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© 2006 American Academy of Allergy, Asthma and Immunology. Published by Elsevier Inc. All rights reserved.
