Pharmacokinetics and tissue distribution of astemizole in the dog

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Abstract
The pharmacokinetics of a single oral dose of 3H‐astemizole (AST) of 1 mg/kg was studied in Beagle dogs and compared with that of a tracer dose superposed at the end of a subchronic experiment. Single and superposed doses were equally well absorbed, and elimination half‐lives of AST and of its metabolites were similar at both occasions (t1/2ß = 3–5 d). Steady‐state was reached after 2–3 weeks of daily dosing. AST and its metabolite desmethylastemizole (DES‐AST) were extensively distributed, mainly to well perfused tissues but only poorly to brain, muscle, and fat. All tissue levels were many times higher than the corresponding plasma concentrations. The superposed tracer dose was well stirred in the tissue compartments and showed instantaneous equilibrium with pretreatment levels. Tissue/plasma level ratios of AST and DES‐AST remained constant with time, indicating that the elimination from tissues proceeded at a similar rate to that from plasma. The extensive distribution of AST and DES‐AST is explained by a strong, but reversible tissue binding that appears to be rate‐limiting for the elimination from the body.