Pharmacokinetic study of nerisopam and its n-acetyl metabolite in rats

Three doses were administered to the rats during the pharmacokinetic study of nerisopam and the plasma concentrations of nerisopam and its N-acetyl metabolite were determined parallelly by means of validated SPE-HPLC method developed by the authors. The pharmacokinetics of nerisopam could be described by a two-compartment open model in rats, it was absorbed rapidly and could be measured in plasma for about 8 hours. The peak plasma concentration of the N-acetyl metabolite was reached rapidly a little bit later than that of the parent compound, similarly to the human plasma, and it could be measured for about 12 hours. The pharmacokinetics of N-acetyl metabolite could be described by an one-compartment open model. The fast appearance of the metabolite and the Cmax and AUC 0-infinity values higher than those of nerisopam refer to an intensive "first-pass" metabolism. The AUC-dose curves indicate that supposingly the mechanism transforming the N-acetyl metabolites are not as fast as the acetylation.