ABSTRACT
A survey of the literature reveals that the pharmacokinetics (PK) and pharmacodynamics (PD) of most antihistamines were investigated simultaneously. In man, the onset and duration of the systemic antihistaminic effect can be determined by measuring the inhibition of the histamine-induced skin wheal and the flare reactions at different time points after single or multiple drug administration. Anticholinergic adverse effects may lead to dry mouth, blurred vision, and urinary retention. After oral intake, the classical antihistamines are reasonably well absorbed with peak plasma concentrations usually being reached between 2–3 h after dosing. Newer antihistamines have been developed which penetrated less through the blood-brain barrier or which showed a lower affinity for brain H1-receptors than for peripheral receptors. Combined PK/PD modeling of the plasma concentration of a new antihistamine and its inhibition of the wheal and flare may provide a better insight into the dose-response relationship so that optimal dosing regimens for further clinical trials can be worked out.
