Rupatadine Oral Solution Titration by Body Weight in Paediatric Patients Suffering from Allergic Rhinitis: A Population Pharmacokinetic Study.

ABSTRACT

BACKGROUND: Allergic rhinitis (AR) and chronic urticaria, both are treated in children with doses of second generation of antihistamines that have been mostly based on extrapolation of data obtained in adults. The objectives of this work were to develop a model to explain the pharmacokinetics (PK) of rupatadine, a second generation antihistamine, administered to children 2-11 years old and to calculate the non-compartmental PK parameters for two groups of age (2-5 and 6-11 years old) based on the individual Bayesian estimates from the selected model. METHODS: Data from two PK studies with rupatadine oral solution (1 mg/mL) were pooled Study A, an extensive blood sampling study performed in 11 children (6-11 years old) who received a single oral dose of rupatadine; and Study B, a sparse blood sampling study in 40 children (2-5 years old) receiving multiple oral doses. A simultaneous population PK model was developed using data available for all children. Using individual Bayesian estimates from the selected model, steady-state plasma concentrations for both studies were simulated and the non-parametric PK parameters were calculated for two age groups 2-5 years (subgroup I) and 6-11 years (subgroup II). RESULTS: A two-compartment model with first-order absorption and elimination with clearance depending on body weight, better described the PK of rupatadine for 2-11 year old children. The plasma clearance dependence on weight was linear. The mean (SD) non-compartment PK parameters calculated using simulated plasma profiles at steady state were Cmax, 2.54 (1.26) vs 1.96 (0.52) ng/mL; AUC0-24h, 10.74 (3.09) vs 10.38 (4.31) ng/mL/h; and t1/2, 12.28 (3.09) vs 15.94 (4.09) h, for children 6-11 and 2-5 years old, respectively. CONCLUSIONS: The PK of rupatadine depends on the weight of paediatric patients but not on their age. The dosage strategy adjusted by body weight in children 2-11 years old (2.5 mL if weight 10-25 kg, and 5 mL if ≥ 25 kg) provides similar exposure between the two groups of age, and to that obtained in adults with the 10 mg dose tablet formulation.