Pharmacokinetic and pharmacodynamic studies of the H 1 ‐receptor antagonist hydroxyzine in the elderly

The pharmacokinetics and pharmacodynamics of the antipruritic H 1 ‐receptor antagonist hydroxyzine hydrochloride were studied in nine healthy, fasting subjects (mean age 69.5 ± 3.7 years) who ingested a single dose of hydroxyzine syrup, 0.7 mg/kg (mean dose 49.0 ± 6.7 mg). Blood samples were collected hourly for 6 hours, every 2 hours from 6 to 12 hours, at 24 hours, and then every 24 hours for 144 hours. At these times an intradermal injection of 0.01 ml of a 0.1 mg/ml histamine phosphate solution was performed, and wheal and flare areas were computed. The serum elimination t ½ of hydroxyzine was 29.3 ± 10.1 hours; the volume of distribution was 22.5 ± 6.3 L/kg; the clearance rate was 9.6 ± 3.2 ml/min/kg, and the AUC was 1383.1 ± 1039.0 ng · hr/ml. The mean serum elimination t ½ of cetirizine, the active metabolite of hydroxyzine generated in vivo, was 24.8 ± 7.7 hours, not significantly different from that of the parent compound (p = 0.05). After a single dose of hydroxyzine the mean wheal and flare areas were significantly suppressed from 1 to 144 hours, compared with the mean predose wheal and flare sizes (p < 0.01). Maximum wheal suppression, compared with all other wheals measured during the study, occurred from 4 to 10 hours, inclusive, and maximum flare suppression occurred from 2 to 72 hours, inclusive (p < 0.01). Hydroxyzine has a long t ½ and a large volume of distribution in the elderly. The suppressive effect on the wheal and flare after a single dose of hydroxyzine is also extremely prolonged, suggesting the possibility of enhanced H 1 ‐receptor activity in old age. Clinical Pharmacology and Therapeutics (1989) 45, 9–14; doi: 10.1038/clpt.1989.2