Pharmacokinetics of acteoside following single dose intragastric and intravenous administrations in dogs / 中国天然药物

Acteoside (verbascoside), a phenylethanoid glycoside widely distributed in various plants, has been shown to have potential activity against Alzheimer's disease, attracting great attentions recently. The present study was designed to develop a selective and sensitive LC-MS/MS method for the determination of acteoside in biological samples and carry our a pharmacokinetic (PK) study in beagle dogs. The PK parameters were calculated using non-compartmental models. Following a single-dose oral administration, acteoside was rapidly absorbed and eliminated, with Tmax being between 30 to 45 min and terminal half-life being about 90 min. The areas under the time-concentration curve (AUC) were 47.28 ± 8.74, 87.86 ± 13.33, and 183.14 ± 28.69 mg · min · L(-1) for oral administration of 10, 20, and 40 mg · kg(-1), respectively, demonstrating that the exposure of acteoside proportionally increased with the dose level. The absolute bioavailability of acteoside was around 4%. For all the PK parameters, there were large variations between individual dogs. In conclusion, the pharmacokinetic characteristics observed in the present study can be of great value to help better understand the pharmacological properties of acteoside and to improve the outcome of its clinical use.

Effect of cyclosporine A on the pharmacokinetics of ginkgolide B in rats / 药学学报

The paper is aimed to investigate the effect of cyclosporine A (CyA) on the pharmacokinetics of ginkgolide B (GB) in rats, and to look for the mechanism of the changes in pharmacokinetic behaviors of GB. GB concentration in plasma, brain homogenate and urine samples of rats was determined by LC-MS. Effects of CyA on plasma levels, brain distributions as well as urinary excretions after intravenous administration of GB were evaluated. CyA co administrated intravenously at 10 mg kg(-1) or 20 mg kg(-1) significantly increased AUC(0-360 min) (P < 0.01) and decreased total CL of GB in rats. While co administrated CYP3A inhibitor itraconazole (ICZ) has no appreciable effect on the pharmacokinetic behavior of GB. CyA increased the brain uptake of GB in a dose-dependent manner. The brain distribution of GB was significantly increased at 5 min by different doses of CyA (P < 0.001), while at 20 and 60 min only high dose of CyA could significantly increase the levels of GB in the brain (P < 0.01 and P < 0.001). Different P-gp inhibitors CyA or verapamil (VER) or digoxin (DGX) decreased the urinary GB excretion, the urinary excretion of GB in 0-8 h were about 34.8% (P < 0.001), 59.4% (P < 0.001) and 79.7% (P < 0.05) of the control, separately. No appreciable effect of ICZ was observed on urinary excretion of GB. Coadministration of P-gp inhibitors CyA could significantly increase the plasma level, accelerate the brain distribution and decrease the urinary excretion of GB.

Study of pharmacokinetics of aristolochic acid I and II in rats / 中国中药杂志

<p><b>OBJECTIVE</b>To develop an HPLC method for determination of the plasma concentration of aristolochic acid I (AA I ) and aristolochic acid II (AA II) and study their pharmacokinetics in rats.</p><p><b>METHOD</b>The plasma samples were extracted with acetonitrile. The analysis involved a C18 column as stationary phase and methanol, water and acetic acid as mobile phase. The flow rate was 1.0 mL min(-1), the UV detection wavelength was 315 nm. After a single intravenous dose of 5 mg kg(-1) AA in rats, the pharmacokinetic parameters were estimated.</p><p><b>RESULT</b>The calibration curve of AA I was linear over the range from 0.056 mg L(-1) to 56.3 mg L(-1) with a correlation coefficient of 0.9997. The mean recovery rate was 88.7%. The RSD of within-day and between-day were all less than 8%. And the calibration curve of AA II was linear over the range from 0.192 mg L(-1) to 11.52 mg L(-1) with a correlation coefficient of 0. 998 9. The mean recovery was 85.8%. The RSD of within-day was less than 3% and between-day was less than 10%. The main pharmacokinetic parameters were estimated to be as follows: CL = (0.010 +/- 0.003) L min(-1) kg(-1), t(1/2alpha) = (8.2 +/- 1.7) min, t(1/2beta) = (79.6 +/- 28.5) min for AA I; CL = (0.003 +/- 0.001) L min(-1) kg (-1), t(1/2alpha) = (56.7 +/- 38.1) min, t(1/2beta) = (209.3 +/- 37.9) min for AA II.</p><p><b>CONCLUSION</b>The established HPLC method is simple and sensitive to determine the concentration of AA I , AA II and the metabolite of AA I in rat plasma. From the result of animal's test, we can find that AA I was quickly eliminated from plasma, the elimination of AA II and Aristololactam-the metabolite of AA I - were slower than that of AA I.</p>