[Astemizole: its pharmacokinetics and pharmacologic properties]

Astemizole (Hismanal) is a chemically novel compound selected from a series of piperidinylaminobenzimidazoles. Further preclinical pharmacological investigations were initiated by experiences with other drugs in the same field. The aim of this review is to illustrate new pharmacological data on astemizole. Astemizole showed the lowest ED50 and the longest duration in mast cell-mediated shock. Binding characteristics to histamine H1 receptors were specificity, selectivity and long duration. Lack of effects on the wakefulness-sleep cycles was evidenced. An equal bioavailability of the drug was demonstrated with different formulations, dosing and food intake. High plasma levels of desmethylastemizole, the major metabolite, and longer half-life than for astemizole, contribute partly to the antihistamine activity. On chronic administration relative amounts of both molecules in the peripheral compartment are most likely responsible for the expected pharmacological effect. The time-course of kinetics shows, the peak plasma levels of the unchanged astemizole followed by a gradual take-over by desmethylastemizole. In patients with hepatic or renal insufficiency the pharmacokinetic background was similar to healthy volunteers.