A simple HPLC method for the quantification of mizoribine in human serum: pharmacokinetic applications.

A simple high-performance liquid chromatographic (HPLC) method was developed and validated for the quantification of mizoribine in human serum. After the addition of 70% perchloric acid and 3-methylxanthine (50 microg/mL, internal standard) to human serum, the samples were mixed and centrifuged at 12,000 rpm (1432 g) for 10 min. The supernatant was injected onto a C(18) column eluted with a mobile phase of 20 mm Na2HPO4 and methanol (93:7, v/v, pH 3) containing 0.04% octanesulfonic acid and detected utilizing an ultraviolet detector at 275 nm. The linear calibration curve was obtained in the concentration range of 0.1-4.0 microg/mL and the lower limit of quantification was 0.1 microg/mL. This method was validated with selectivity, linearity, precision and accuracy. In addition, the method was successfully applied to estimate the pharmacokinetic parameters of mizoribine in Korean subjects following an oral administration of 100 mg mizoribine (two Bredinine 50 mg tablets). The maximum serum concentration (C(max)) of 2.30 +/- 0.83 microg/mL was reached 2.27 +/- 0.66 h after an oral dose. The mean AUC(0-12 h) and the elimination half-life (t(1/2)) were 13.2 +/- 4.79 microg h/mL and 3.10 +/- 0.74 h, respectively.

Effects of silymarin and formulation on the oral bioavailability of paclitaxel in rats.

The aims of the present study were to investigate the effects of silymarin, an inhibitor of the P-glycoprotein efflux pump, on oral bioavailability of paclitaxel in rats, and to compare pharmacokinetic parameters of paclitaxel between a commercial formulation of paclitaxel (Taxol®) and a paclitaxel microemulsion. Oral bioavailability of paclitaxel in a Taxol® formulation was enhanced in the combination with silymarin (10 and 20mg/kg). In particular, the mean maximum plasma concentration (C(max)) and the mean area under the plasma concentration-time curve (AUC(0-)(t)) of paclitaxel in the Taxol® formulation were significantly increased 3-fold and 5-fold compared with control, respectively, following oral co-administration with 10mg/kg of silymarin (p<0.01). When the paclitaxel microemulsion was co-administered with silymarin (20mg/kg) orally, it caused a maximum increase in the absolute bioavailability of paclitaxel (19%). In addition, the relative bioavailability of the paclitaxel microemulsion was 184% as compared to Taxol® after oral dosing, whereas the mean time required to reach C(max) (T(max)) of paclitaxel was decreased in the microemulsion formulation compared with Taxol®, suggesting faster absorption. Based on these results, we conclude that oral bioavailability of paclitaxel is significantly improved by co-administration with silymarin, an inhibitor of the P-gp efflux pump and by microemulsion formulation.