Dose‐proportionality, bioavailability, and steady‐state kinetics of astemizole in man

The pharmacokinetics and dose-proportionality of astemizole (AST) (10, 20, and 30 mg given orally) were studied in 12 healthy male subjects by radioimmunoassay after selective extraction, enabling the determination of the plasma levels of AST and its major metabolite desmethylastemizole (DES-AST). Peak levels of AST were reached within 1 hr. Plasma levels decayed biphasically with terminal half-lives of about 1 day for AST and about 10 days for DES-AST. Areas under the curve of parent drug accounted for 5% of those of DES-AST. The bioavailability/bioequivalence of AST was studied in 21 healthy subjects according to a three-way cross-over design. Subjects received orally 30-mg doses as a tablet, suspension, or solution. The study demonstrated an equal bioavailability of the drug from the three formulations since rate and extent of absorption were not significantly different. In patients with perennial allergic rhinitis, treated for 20 weeks with AST 10 mg/day, steady-state was reached within 1 week for AST and within 4 weeks for DES-AST. Elimination half-lives after chronic treatment were similar to those after single dosing. Steady-state plasma levels were in close agreement with predicted levels, indicative of linear pharmacokinetics of AST in man.