An in vitro study on interaction of anisodine and monocrotaline with organic cation transporters of the SLC22 and SLC47 families / 中国天然药物

Current study systematically investigated the interaction of two alkaloids, anisodine and monocrotaline, with organic cation transporter OCT1, 2, 3, MATE1 and MATE2-K by using in vitro stably transfected HEK293 cells. Both anisodine and monocrotaline inhibited the OCTs and MATE transporters. The lowest IC was 12.9 µmol·L of anisodine on OCT1 and the highest was 1.8 mmol·L of monocrotaline on OCT2. Anisodine was a substrate of OCT2 (K = 13.3 ± 2.6 µmol·L and V = 286.8 ± 53.6 pmol/mg protein/min). Monocrotaline was determined to be a substrate of both OCT1 (K = 109.1 ± 17.8 µmol·L, V = 576.5 ± 87.5 pmol/mg protein/min) and OCT2 (K = 64.7 ± 14.8 µmol·L, V = 180.7 ± 22.0 pmol/mg protein/min), other than OCT3 and MATE transporters. The results indicated that OCT2 may be important for renal elimination of anisodine and OCT1 was responsible for monocrotaline uptake into liver. However neither MATE1 nor MATE2-K could facilitate transcellular transport of anisodine and monocrotaline. Accumulation of these drugs in the organs with high OCT1 expression (liver) and OCT2 expression (kidney) may be expected.

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.

A novel pulmonary delivery system--dry powder inhalers / 药学学报

Dry powder inhalers (DPIs) have received considerable attention because of their propellant-free composition and stability. DPIs include the DPI devices and inhalation powders. The purpose of this review is to address the development of the DPIs, including the mechanisms of absorption, the products, the devices, the preparation technology, and the characteristics.

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>

Research on minimal to mild endometriosis associated infertility / 浙江大学学报·医学版

Endometriosis is a common disease of reproductive age women and infertility is one of its clinical manifestations. Infertility of patients with severe endometriosis may be attributed to the anatomy alteration of pelvis.However, the infertility of patients with minimal to mild endometriosis whose pelvic anatomy remains intact is still hard to explain. It is considered that the infertility of patients with ninimal to mild endometriosis is associated with the alteration of the pelvic microenvironment. Several kinds of cytokines and proteins are involved in this process. They may disturb steps necessary to achieve successful pregnancy, such as ovulation,gamete transport, fertilization, embryo transport and implantation. Any disturbance to one of the steps mentioned above may lead to pregnant loss.

Preparation of verapamil hydrochloride controlled-onset extended-release pellets and its pharmacokinetics in dogs / 药学学报

<p><b>AIM</b>To prepare verapamil hydrochloride controlled-onset extended-release pellets (VH-COERP) and study its release behavior in vitro. To compare the pharmacokinetic characteristics and bioavailability in six Beagle dogs after oral administration of VH-COERP and verapamil hydrochloride delayed-release pellets (VH-DRP) as reference.</p><p><b>METHODS</b>The core of VH-COERP were prepared in the fluidized bed (mini-glatt) by spraying water solution containing drugs onto sucrose-starch pellets with hydroroxy propyl methyl cellulose (HPMC) as the inner coating swelling layer and ethylcellulouse aqueous dispersion as the outer coating controlled layer. Through modifying the coating level of inner and outer layer, the VH-COERP with the optimized cumulative release profile was obtained. The concentration of VH in plasma of six dogs and its pharmacokinetic behaviors after oral administration of VH-COERP and VH-DRP at different times were studied by RP-HPLC. The pharmacokinetic parameters were computed by software program 3P97.</p><p><b>RESULTS</b>The lag time, the release behavior and the amount of VH from VH-COERP within 24 hours were not influenced by the pH of dissolution medium and post-process, but obviously influenced by the different kinds of added material in swelling layer and the coating level of the inner swelling layer and the outer controlled layer. In vitro the lag time of release profile of VH from VH-COERP was 5 h and then VH was extended release from VH-COERP in the following time. Compared with the VH-DRP, VH-COERP in vivo has an obviously lag time (4 h) , Tmax was also delayed (8 h) and the relative bioavailability was (94.56 +/- 7.64)%.</p><p><b>CONCLUSION</b>The release profile of VH from VH-COERP was shown to be extended-release after an conspicuous lag time in vitro and in vivo. So the drug can be taken by the patient before bed time and begin to work at the morning.</p>

HPLC determination of insulin and its related substances in insulin powder for inhalation / 药学学报

<p><b>AIM</b>To determine insulin and its related substances in insulin powder for inhalation by reversed phase high performance liquid chromatography method.</p><p><b>METHODS</b>The initial mobile phase was solution A (0.1% trifluoroacetic acid-acetonitril 70:30) and changed to solution B (0.1% trifluoroacetic acid-acetonitril 60:40) in 30 minutes. The flow rate was 2.0 mL.min-1, the column temperature was 30 degrees C, the wave length was 280 nm, the injected volume was 20 microL.</p><p><b>RESULTS</b>Insulin was well separated from other peaks induced in different conditions. There was good linear relationship between the amount of insulin and its peak area, the RSD was 1.1%, the insulin solution for determination was stable in 12 hours, and the quantity detected was near the added.</p><p><b>CONCLUSION</b>The method is simple and accurate to detect insulin and its related substances in insulin and its preparations.</p>