Abstract
We studied the pharmacokinetics and the suppression of histamine-induced wheals, flares, and pruritus in the skin after administration of the histamine H 1 antagonist hydroxyzine to seven healthy adults. After a single oral dose of hydroxyzine, 0.7 mg/kg (mean dose 39.0 ± 5.4 mg), the mean maximum serum hydroxyzine concentration of 72.5 ± 11.1 ng/ml occurred at a mean time of 2.1 ± 0.4 hr. The mean elimination half-life calculated from the terminal linear portion of the serum hydroxyzine concentration vs. time curve was 20.0 ± 4.1 hr. The mean clearance rate was 9.78 ± 3.25 ml/min/kg and the mean volume of distribution was 16.0 ± 3.0 L/kg. The single dose of hydroxyzine suppressed pruritus at the wheal and flare sites from 1 to 36 hr. Maximal suppression of the wheals was 80% and maximal suppression of the flare was 92%. Significant suppression of the wheals and flares persisted for 36 and 60 hr. respectively. Pharmacodynamic analysis of the wheal and flare suppression data and the mean serum hydroxyzine concentrations supports the prolonged terminal serum half-life value for the drug.
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