The pharmacokinetics and pharmacodynamics of terfenadine in children

Area of Science:

• Pediatric Allergy and Immunology
• Clinical Pharmacology
• Drug Metabolism and Pharmacokinetics

Background:

• Allergic rhinitis is a common condition in children, impacting quality of life.
• Understanding the pharmacokinetics and pharmacodynamics of antihistamines is crucial for effective pediatric treatment.
• Terfenadine is a widely used antihistamine, but its pediatric profile requires specific investigation.

Purpose of the Study:

• To investigate the pharmacokinetics and pharmacodynamics of terfenadine in children with allergic rhinitis.
• To determine the serum concentrations and half-life of terfenadine's active metabolite.
• To assess the efficacy of terfenadine in suppressing histamine-induced skin reactions.

Main Methods:

• A single-dose pharmacokinetic and pharmacodynamic study was conducted in 13 children (mean age 7.45 years) with allergic rhinitis.
• Serum concentrations of terfenadine metabolite I were measured hourly for 8 hours post-administration.
• Epicutaneous tests with histamine phosphate were performed to evaluate wheal, flare, and itching suppression.

Main Results:

• The mean maximum serum concentration of terfenadine metabolite I was 242 ng/ml, occurring at 2.3 hours, with a mean half-life of 2.0 hours.
• Significant suppression of histamine-induced wheals and flares was observed from 1 to 8 hours post-dose.
• Complete suppression of itching occurred for 8 hours, with no serious adverse effects reported.

Conclusions:

• Terfenadine is well-absorbed in children, and its active metabolite exhibits a short serum elimination half-life.
• The duration of terfenadine's suppressive effect on histamine-induced skin reactions significantly exceeds predictions based on metabolite concentrations.
• These findings support the efficacy and safety of terfenadine for managing allergic rhinitis symptoms in pediatric populations.