Pharmacokinetics and pharmacodynamics of cetirizine in infants and toddlers
1Hospital Bulovka, Prague.
Insights
Cetirizine pharmacokinetics in infants show a short elimination half-life, but skin histamine inhibition lasts longer than expected. This suggests prolonged H1-receptor blockade in young children.
Area of Science:
- Pharmacology
- Pediatric Medicine
- Clinical Pharmacy
Background:
- Second-generation H1-receptor antagonists like cetirizine are commonly used for allergic conditions.
- Limited pharmacokinetic data exists for cetirizine in infants and toddlers.
- Understanding drug disposition and effect duration in this age group is crucial for safe and effective treatment.
Purpose of the Study:
- To characterize the pharmacokinetics of a single dose of cetirizine in infants and toddlers.
- To evaluate the pharmacodynamic effect (H1-inhibition) of repeated cetirizine dosing in this population.
- To compare the duration of H1-inhibition with pharmacokinetic parameters.
Main Methods:
- 15 infants and toddlers received a single 0.25 mg/kg dose of cetirizine solution.
- Blood and urine samples were collected over 24 hours to determine pharmacokinetic parameters.
- A pharmacodynamic study assessed histamine-induced wheal and flare inhibition after 4 days of twice-daily dosing in 10 participants.
Main Results:
- Peak plasma levels of cetirizine were observed at 2.0 hours.
- The elimination half-life was 3.1 hours, with 62.7% of the dose excreted unchanged in urine.
- Significant inhibition of wheal (90%) and flare (87%) persisted 12 hours after the last dose, similar to older age groups.
Conclusions:
- Cetirizine exhibits rapid absorption and elimination in infants and toddlers.
- Despite a short pharmacokinetic half-life, cetirizine provides prolonged H1-receptor inhibition at the skin level in this age group.
- The duration of H1-inhibition suggests a longer clinical effect than predicted by pharmacokinetics alone.
Abstract:
The pharmacokinetics of the second generation H1-receptor antagonist cetirizine were studied in 15 infants and toddlers (mean +/- SD age, 12.3 +/- 5.4 months) who were treated with a single 0.25 mg/kg dose of cetirizine solution. The infants and toddlers were hospitalized for recurrent respiratory infections or other hypersensitivity-related diseases. Blood samples were collected at 1/2, 1, 11/2, 2, 4, 6, 8, 12, and 24 hours, and a 24-hour urine sample was obtained. A peak plasma level of 390 +/- 135 ng/ml was observed after 2.0 +/- 1.3 hours. The elimination half-life was 3.1 +/- 1.8 hours, the apparent oral body clearance was 2.13 +/- 1.15 ml/min/kg, and the apparent volume of distribution was 0.44 +/- 0.19 L/kg. The excretion of unchanged cetirizine in six complete urinary collections was 62.7% +/- 13.2% of the administered dose. An additional pharmacodynamic study (inhibition of the histamine-induced wheal and flare) was performed in 10 of these infants and toddlers, after the intake of 0.25 mg/kg cetirizine twice a day for at least 4 days. A 90% +/- 12% inhibition of the wheal and a 87% +/- 17% inhibition of the flare were still observed 12 hours after the last intake. The duration of the H1-inhibition by cetirizine at the cutaneous level is thus longer in infants and toddlers than could be inferred from its pharmacokinetics; the level of inhibition at 12 hours was the same as in older age groups.
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