[Pharmacokinetics and metabolism of tofizopam (Grandaxin)]

Present publication summarizes the pharmacokinetics and metabolism investigations of anxiolytic tofizopam (Grandaxin) carried out in Hungary and in other countries. The pharmacokinetics and metabolism of tofizopam were studied in animals (mice, rat, rabbit, dog, monkey) and humans. The pharmacokinetics profile of the compound can be described by a two-compartment open model, where the absorption and distribution phase were found to be rapid (tmax 0.5-1.0 hour in rats and 1.0-1.5 hours in humans). The unchanged tofizopam and 14C-total radioactivity were eliminated from human plasma with a biological half-life (t beta 1/2) of 2.7-3.5 hours and 15-21 hours, respectively, which show a slower elimination of the metabolites. The main route of elimination was the excretion of the mainly conjugated metabolites after the intensive first-pass metabolism in urine and/or faeces, depends on the species. The major route of biotransformation was mono-, di-, tri- and tetra-o-demethylation in the various degree and positions of aromatic ring(s).