Pharmacokinetics and pharmacodynamics of terfenadine and chlorpheniramine in the elderly.
In a double-blind, randomized, crossover study, the H1-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 less than 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 H1-receptor-antagonist ingestion.
Simons
K J
KJ
Health Sciences Clinical Research Center, Faculty of Pharmacy, University of Manitoba, Winnipeg, Canada.
Martin
T J
TJ
Watson
W T
WT
Simons
F E
FE
D000368:Aged; D000375:Aging / Q000187:drug effects* / Q000502:physiology; D001559:Benzhydryl Compounds / Q000097:blood / Q000493:pharmacokinetics* / Q000494:pharmacology; D002744:Chlorpheniramine / Q000097:blood / Q000493:pharmacokinetics* / Q000494:pharmacology; D002851:Chromatography, High Pressure Liquid; D004311:Double-Blind Method; D005260:Female; D006207:Half-Life; D006801:Humans; D016032:Randomized Controlled Trials as Topic; D012882:Skin Tests; D016593:Terfenadine; D013997:Time Factors
D001559:Benzhydryl Compounds; D002744:Chlorpheniramine; D016593:Terfenadine