Pharmacokinetics and pharmacodynamics of terfenadine and chlorpheniramine in the elderly

In a double-blind, randomized, crossover study, the H 1-receptor antagonists, terfenadine and chlorpheniramine, were investigated in eight healthy, fasting female subjects, aged 67.8 ± SD 0.8 years, who ingested single doses of terfenadine, 1 mg/kg (mean dose, 69.6 ± 11.2 mg), and chlorpheniramine, 0.12 mg/kg (mean dose, 8.4 ± 1.3 mg). The mean serum-elimination half-life of terfenadine metabolite I was 8.7 ± 3.7 hours. After terfenadine ingestion, significant wheal suppression occurred from 2 to 24 hours compared to predose wheal size, with maximum wheal suppression, 42 ± 13% to 60 ± 16% from 2 to 12 hours. Significant flare suppression occurred from 2 to 24 hours, with maximum flare suppression, 75 ± 15% to 78 ± 13% from 4 to 8 hours. The mean serum-elimination half-life of chlorpheniramine was 22.6 ± 11.0 hours. After chlorpheniramine ingestion, significant wheal suppression occurred from 1 to 10 hours, inclusive, compared to predose wheal size, with maximum wheal suppression, 36 ± 11% to 37 ± 11% from 5 to 6 hours. Significant flare suppression occurred from 1 to 12 hours, with maximum flare suppression of 43 ± 14% to 46 ± 19% at 2, 5, and 6 hours ( p < 0.01). Adverse effects, chiefly sedation, occurred in five of eight patients after receiving terfenadine, and in all eight patients after receiving chlorpheniramine; but, since no placebo control was administered, these adverse effects could not be definitely attributed to H 1-receptor-antagonist ingestion.