The pharmacokinetics of orally administered fudosteine in healthy Chinese volunteers

The pharmacokinetics of fudosteine in healthy Chinese volunteers was investigated for the first time after single- and multiple-dose administration. Five male and five female volunteers were enrolled in this study. Each subject received 400 mg fudosteine capsules (the therapeutic dose) on day 1 after overnight fasting for the single-dose study and three times daily oral administration (400 mg) for 5 consecutive days until the sixth morning for the multiple-dose study. Serial blood samples were collected at specified time intervals up to 16 hours following the first and last doses of fudosteine. Plasma harvested from the blood was separated and analyzed for fudosteine levels by a validated high-performance liquid chromatography-electrospray ionization mass spectrometry (HPLC/ESI/MS) method employing percolumn derivatization with 9-fluorenylmethyl chloroformate (FMOC-Cl). Noncompartmental analysis was used for the calculation of the total area under the plasma concentration-time curve (AUC) from time zero to time infinity and the terminal half-life (t(1/2)) of fudosteine. The pharmacokinetic parameters for single- and multiple-dose administration were estimated as follows: C-max amounted to 10.13 +/- 4.39 mu g/mL and 11.75 +/- 6.51 mu g/mL, t(max) to 0.69 +/- 0.36 h and 0.53 +/- 0.12 h and t(1/2) to 2.33 +/- 0.63 h and 2.40 +/- 0.37 h, respectively. No significant differences were found between single- and multiple-dose oral administration, although gender differences were observed.