Peripheral antihistamine and central sedative effects of single and continuous oral doses of cetirizine and hydroxyzine

Summary

The peripheral histamine-inhibiting and central sedative effects of single oral doses (SOD) and of repeated administration for one week (steady state, SS), of 20 mg hydroxyzine HCL and 10 mg cetirizine have been assessed in 12 healthy volunteers, in a double-blind placebo-controlled cross-over study. Peripheral H₁-receptor antagonism was estimated as the reduction in the area of the flare and the duration of the itch after intradermal injection of histamine 0.1 and 1.0 μg. CNS effects were assessed by a battery of computerized neuropsychological tests and seven visual analogue scales. Drug compliance was ascertained by plasma level determinations.

Cetirizine 10 mg (SOD) produced a more pronounced peripheral effect than 20 mg hydroxyzine, whereas hydroxyzine but not cetirizine, showed a significant sedative action in the relevant rating scales. These effects vanished during steady state, suggesting adaptation to the initial sedative effect of hydroxyzine in most of the subjects.

No sedative effect of cetirizine was demonstrated. There was no impairment at group level in the neuropsychological tests after the SOD or SS treatment. However, six subjects who showed sedation in the analogue ratings after hydroxyzine, displayed significantly impaired performance after hydroxyzine SOD.

The findings are discussed in relation to the individual characteristics of the study groups.