[Human pharmacokinetic study of nerisopam and its n-acetyl metabolite]

It was established during the human phase I study of nerisopam, a new anxiolytic drug, that nerisopam (EGIS-6775) shows two, while N-acetyl metabolite (EGIS-7649) shows one compartmental pharmacokinetic behaviour. Acetylation of nerisopam is polymorph, so that volunteers belonging into slow or fast acetylating group show significantly different plasma concentration. Observed pharmacokinetic differences are primarily manifested in the absorption phase, and not in the elimination one. Accordingly, slow acetylators have higher nerisopam levels, while fast acetylators possess higher metabolite levels. Elimination phase is practically parallel for both compounds. At the same time, significant differences are found in the AUC and Cmax values. Nerisopam is rapidly absorbed, but N-acetyl metabolite is appeared especially fast in the blood. Our consideration is, that nerisopam undergoes significant "first-pass" metabolism process, the extent of which is different between the two acetylator phenotypes.