The pharmacokinetic profiles of the second generation antihistamines have been well studied in adults. All three agents have a rapid onset of action, with a time to maximum concentration averaging 1 to 2 hours. Administration with food causes a delay in absorption that is not believed to be clinically significant. Cetirizine and fexofenadine are primarily excreted as unchanged drug, with average elimination half-lives in adults of 8 and 14 hours, respectively. Loratadine undergoes hepatic metabolism through the cytochrome P450 enzyme system, with an average half-life of 8 to 28 hours for the parent drug and active metabolites.
Children appear to have a more rapid elimination of cetirizine than adults. In a study of 15 infants and toddlers (age range 6 to 23 months) given a single cetirizine dose of 0.25 mg/kg, Spicak and colleagues found an average elimination half-life of 3.1±1.8 hours, with an apparent oral clearance of 2.13±1.15 ml/min/kg and an apparent volume of distribution of 0.44±019 L/kg. Approximately 67% of the dose was excreted unchanged. In a study of 2-6 year old children given a 5 mg oral dose, elimination half-life was 5.55±0.98 hours, with an apparent clearance of 1.27±0.80 ml/min/kg and an apparent volume of distribution of 0.60±0.38 L/kg. Despite this more rapid elimination, duration of effect was similar to that of adults, so that no change in dose appears to be needed.
Pharmacokinetic studies of both fexofenadine and loratadine in children have provided results similar to those in adults. Fexofenadine pharmacokinetic parameters were evaluated in a study of 14 children (mean age 9.8+1.8 years). The patients were given a single 30 or 60 mg oral dose. Average elimination half-lives were 18.3±2.0 and 17.6±1.0 hours, for the 30 and 60 mg doses, respectively, and were comparable to adult values. The pharmacokinetics of loratadine were studied in 18 children (ages 2-5 years). Each patient was given a single 5 mg oral dose. Time to maximum concentration averaged 1.17±0.38 hours with an area under the curve for the desloratadine metabolite of 61.4±25.4 ng hr/ml, similar to values for adults.
Pediatr Pharm. 2001;7(4) © 2001 Children's Medical Center, University of Virginia
Cite this: The Second-Generation (Peripherally-Selective) Antihistamines in Children - Medscape - Apr 01, 2001.