The time course of action of three differing doses of noberastine, a novel H1-receptor antagonist, on histamine-induced skin wheals and the relationship to plasma drug concentrations in normal human volunteers.

1. The time course and magnitude of effect of the novel H1-receptor antagonist noberastine, structurally modified from astemizole to achieve a more rapid onset while retaining a good duration of action, has been investigated using histamine-induced skin wheals in healthy volunteers. 2. The pharmacokinetics and pharmacodynamics of three doses (10, 20 and 30 mg) have been studied in a double-blind, placebo controlled, randomised cross-over trial involving 12 healthy male volunteers. 3. All doses of noberastine caused inhibition of histamine-induced skin wheals, which were significantly different from placebo (P < 0.0001) when assessed as the area under the percent inhibition of the response vs time curves. 4. Following single dose administration of 10, 20 and 30 mg noberastine significant inhibition of histamine-induced skin wheals occurred and this effect persisted beyond 24 h. 5. At the higher (20 and 30 mg) doses studied significant inhibition of the histamine-induced skin wheal occurred by 1 h of dosing, whereas this did not occur until 2 h following the 10 mg dose. 6. An increase in plasma concentrations of noberastine was seen after administration of all doses, with mean (s.d.) concentrations of 4.14 (3.70), 8.38 (7.81) and 12.66 (11.82) ng ml-1 1 h following administration of 10, 20, and 30 mg respectively. 7. Visual analogue scale measurements of drowsiness identified no sedative effects above those of placebo at any of the dose levels. 8. We conclude that noberastine is an effective H1-receptor antagonist in the human as assessed by its effect on histamine-induced skin wheals.