Diphenhydramine: pharmacokinetics and pharmacodynamics in elderly adults, young adults, and children

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Diphenhydramine: pharmacokinetics and pharmacodynamics in elderly adults, young adults, and children

KJ Simons, WT Watson, TJ Martin, XY Chen, and FE Simons

The pharmacokinetics and pharmacodynamics of the H1-receptor antagonist diphenhydramine were studied in 21 fasting subjects divided into three age groups: elderly, (mean age 69.4 +/- 4.3 years), young adults, (mean age 31.5 +/- 10.4 years), and children, (mean age 8.9 +/- 1.7 years). All subjects ingested a single dose of diphenhydramine syrup 1.25 mg/kg, in mean doses of 86.0 +/- 7.3 mg, 87.9 +/- 12.4 mg, and 39.5 +/- 8.4 mg, respectively. Blood samples were collected hourly for 6 hours, every 2 hours until 12 hours, at 24 hours, and, in the adults, up to 72 hours after diphenhydramine administration. At these times, histamine skin tests were performed and wheal and flare areas were computed. The mean serum elimination half-life values for diphenhydramine differed significantly in elderly adults, young adults, and children, with values of 13.5 +/- 4.2 hours, 9.2 +/- 2.5 hours, and 5.4 +/- 1.8 hours being found respectively in each age group. Clearance rates for diphenhydramine also differed significantly with age, being 11.7 +/- 3.1 mL/min/kg in elderly adults, 23.3 +/- 9.4 mL/min/kg in young adults and 49.2 +/- 22.8 mL/min/kg in children. Diphenhydramine produced a maximum wheal suppression of 39.6 +/- 22.5% and a maximum flare suppression of 46.5 +/- 32.1% at 5 and 6 hours respectively in the elderly; a maximum wheal suppression of 45.5 +/- 25.0% and a maximum flare suppression of 53.4 +/- 16.9% at 6 and 4 hours respectively in young adults; and a maximum wheal suppression of 68.4 +/- 10.2% and a maximum flare suppression of 87.2 +/- 4.2% at 2 hours in children.
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