Advances in cardiovascular effects of tanshinone II(A) / 中国中药杂志

Cardiovascular diseases, like coronary heart disease and myocardial infarction, are the most common cause of death worldwide. Chinese medicines have demonstrated rich cardioprotective activities for clinical applications. Salvia miltiorrhiza, a very important component of traditional Chinese medicine, can promote blood circulation and relieve blood stasis. Salvia miltiorrhiza is widely used in treatment of cardiovascular and cerebrovascular disease such as coronary heart disease and cerebral infarction ( CI). Tanshinone II(A), the major lipophilic components extracted from the root of S. miltiorrhiza, possesses anti-atherosclerosis, anti-cardiac hypertrophy, anti-oxidant, anti-arrhythmia and so on. This paper discusses current research status of tanshinone II(A) in cardioprotective effects.

Progress on mechanism of Tripterygium wilfordii-induced liver injury and detoxification mechanism of licorice / 中国中药杂志

Tripterygium wilfordii has exihibited multiple pharmacological activities, such as anti-inflammatory, immune modulation, anti-tumor and anti-fertility. T. wilfordii have been used for the therapy of inflammation and autoimmune diseases including rheumatoid arthritis, immune complex nephritis and systemic lupus erythematosus clinically. However, it is well known that T. wilfordii has small margin between the therapeutic and toxic doses and could cause serious injury on digestive, reproductive and urogenital systems. Among all the organs, liver is one of the most remarkable targets of T. wilfordii-induced toxicities, and the damage is more serious than others. It is generally accepted that T. wilfordii-induced liver injury is a result of the combined effects of toxic elements of T. wilfordii. It is reported in several studies that the mechanism of T. wilfordii-induced liver injury may be related to lipid peroxidation, cell apoptosis and immune damage, and so on. Licorice is one of the most commonly used Chinese herbal medicine, with effects of heat- clearing and detoxicating, anti-inflammatory and hepatoprotective, reconciling various drugs, and so on. Licorice often accompany T. wilfordii in clinical application which can significantly reduce the liver injury induced by T. wilfordii. The attenuated effect is exact, but the mechanism is still a lack of in-depth study. This paper reviews the studies on T. wilfordii-induced liver injury and the related mechanism as well as licorice and other traditional Chinese medicine accompany T. wilfordii to reduce the injury in recent years, so as to provide reference for related research in the future.

Modeling and simulation activities to design sampling scheme for population pharmacokinetic study on amlodipine / 药学学报

Reasonable sampling scheme is the important basis for establishing reliable population pharmacokinetic model. It is an effective method for estimation of population pharmacokinetic parameters with sparse data to perform population pharmacokinetic analysis using the nonlinear mixed-effects models. We designed the sampling scheme for amlodipine based on D-optimal sampling strategy and Bayesian estimation method. First, optimized sample scenarios were designed using WinPOPT software according to the aim, dosage regimen and visit schedule of the clinical study protocol, and the amlodipine population model reported by Rohatagi et al. Second, we created a NONMEM-formatted dataset (n = 400) for each sample scenario via Monte Carlo simulation. Third, the estimation of amlodipine pharmacokinetic parameters (clearance (CL/F), volume (V/F) and Ka) was based on the simulation results. All modeling and simulation exercises were conducted with NONMEM version 7.2. Finally, the accuracy and precision of the estimated parameters were evaluated using the mean prediction error (MPE) and the mean absolute error (MAPE), respectively. Among the 6 schemes, schemes 6 and 3 have good accuracy and precision. MPE is 0.1% for scheme 6 and -0.6% for scheme 3, respectively. MAPE is 0.7% for both schemes. There is no significant difference in MPE and MAPE of volume among them. Therefore, we select scheme 3 as the final sample scenario because it has good accuracy and precision and less sample points. This research aims to provide scientific and effective sampling scheme for population pharmacokinetic (PK) study of amlodipine in patients with renal impairment and hypertension, provide a scientific method for an optimum design in clinical population PK/PD (pharmacodynamics) research.

RP-HPLC study of resveratrol derivative (BTM-0512) in rat plasma and tissue distribution / 药学学报

This paper described a rapid and sensitive HPLC method to analyze (E)-3,5,4'-trimethoxystilbene (BTM-0512) in rat plasma and tissues. The analysis used a BDS Hypersil C18 analytical column (250 mm x 4.6 mm ID, 5 microm) and acetonitrile/water as the mobile phase. The UV detection wavelength was 319 nm. Proteins were precipitated with acetonitrile and diethylstilbestrol as internal standard. The method was validated according to State Food and Drug Administration of China and ICH of Technical Requirements for Registration of Pharmaceuticals for Human Use Guidelines. The limit of detection (S/N: 3/1) for BTM-0512 was 0.005 microg x mL(-1) for plasma. The method performances were shown to be selective for BTM-0512 and the linearity of the assay method was up to 10.0 microg x mL(-1) and 40.0 microg x g(-1) for plasma and tissues, respectively. At 0.1, 1 and 5 microg x mL(-1) (n=5), intraday and interday precision values (% RSD) were in the range of 2.6% - 5.1% and 2.4% - 4.8%, respectively. Mean accuracy and absolute recoveries of BTM-0512 ranged from 95.3% - 100.1% and 95.9% - 100.9% for plasma and tissues, respectively. This method can be quite useful for BTM-0512 pharmacokinetic and tissue distribution studies, for purpose which multiple plasma and tissue samples can be analyzed quickly with high reproducibility.