Diphenhydramine: Pharmacokinetics and Pharmacodynamics in Elderly Adults, Young Adults, and Children

Abstract

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.

Survival after Diphenhydramine Ingestion with Hemodialysis in a Toddler

“…Diphenhydramine has rapid absorption, with peak blood and tissue concentrations 2 h after ingestion of oral tablets [5]. In the case presented, the ingestion of liquid gelcaps had onset of symptoms within 30 min.…”

“…In the case presented, the ingestion of liquid gelcaps had onset of symptoms within 30 min. The half-life in children has been estimated to be 5.4±1.8 h [5] and may be prolonged in overdose. Severe symptoms, including coma, seizures, and dysrhythmias, appear to be more likely with ingestions over 1.0 to 1.5 g in adults or approximately 15-20 mg/kg in children [6].…”

Levocetirizine: Pharmacokinetics and pharmacodynamics in children age 6 to 11 years

“…3 Most of the orally administered H 1 -antihistamines are available in dosage formulations suitable for administration to children and even to infants; however, only 11 of the 40 H 1 -antihistamines have been studied prospectively in children with regard to their pharmacokinetics and pharmacodynamics. [4][5][6][7][8][9][10][11][12][13][14][15][16][17][18][19][20][21][22][23] These studies have generally been conducted after administration of a single dose, 5-10,12-20 but 3 studies have been performed at steady state, 11,12,20 and in a few studies, a population pharmacokinetic design [21][22][23] has been used. The clinical pharmacology of a few of the first-generation H 1 -antihistamines, such as chlorpheniramine, brompheniramine, diphenhydramine, and hydroxyzine, was investigated after they had been used in children for several decades.…”

Hypnotic use and fatigue in multiple sclerosis

“…more than half of CNS histamine receptors within 90 min of administration [24]. The elimination half-life of diphenhydramine is 4-9 h for healthy adults, but may be increased in patients with hepatic impairment, and in the elderly [25,26]. Sedation may be a primary desired effect for patients who use antihistamines, but carryover symptoms -including decreased mental alertness and impaired daytime psychomotor performance -are common side effects.…”