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Recently the Salvia Miltiorrhiza–Moutan Cortex (SM‐MC) herb pair is considered as a promising Chinese medicinal mixture exhibiting a range of pharmacological activities, including treating cardiovascular disease due to its unique composition. In this study, we conducted the comparative pharmacokinetic analysis of seven main bioactive components of SM‐MC in a different model rat. A straightforward ultra‐performance liquid chromatography–tandem mass spectrometry (UPLC‐MS/MS) strategy that could simultaneously evaluate the levels of seven compounds was used to ensure the reliability of these pharmacokinetic analyses in rat plasma. The rat plasma samples were collected from normal, sham‐operated, and myocardial ischemia–reperfusion injury (MIRI) groups at predetermined time points after the administration of SM‐MC. The main pharmacokinetic parameters were detected and calculated. We successfully assessed the maximum concentration (Cmax), time to Cmax (Tmax), the elimination rate constant (λz), total half‐life (t1/2), total body clearance (CL), and the area under the concentration–time curve from 0 to last sampling time (AUC0–t) and extrapolated to infinity (AUC0–∞). To sum up, an optimized UPLC‐MS/MS approach that could be used to rapidly, simultaneously, and sensitively detect seven bioactive compounds derived from SM‐MC extract preparations was successfully developed, which may offer a pharmacokinetic basis for preclinical and clinical studies of SM‐MC herb pair for treating MIRI. [ABSTRACT FROM AUTHOR]

Objective; To introduce the hazard vulnerability assessment (HVA) method to the risk management of high-alert drugs, and also to analyze the hospital's ability to withstand high-alert drug risk factors, so as to clarify the priorities and make useful explorations for the hospital's control of high-alert drugs. Methods : The HVA method was used to identify and evaluate the potential risk events for high-alert drugs in the hospital, and then the risk assessment items were assessed and ranked in order, so as to identify high risk events demanding top priority management. Results : There were 13 risk items in the management and control of high-alert drugs in the hospital, of which 2 items were of moderate risk level, i. e. the prescription dosage error and neglect of error prescriptions in prescription review, and other items were of all low risk level. Conclusion : The HVA method could be applied to the management of high-alert drugs in the hospital. Specific contermeasures to strengthen risk management in accordance with risk factors could not only reduce the risk of safe drug use caused by hazard vulnerability of high-alert drugs, but also provide assistance for safe and effective management of high-alert drugs. [ABSTRACT FROM AUTHOR]

Multidrug resistance(MDR) is a major obstacle to efficiency of breast cancer chemotherapy. We investigated whether combination of metformin and 2-deoxyglucose reverses MDR of MCF-7/Dox cells and tried to elucidate the possible mechanisms. The combination of metformin and 2-deoxyglucose selectively enhanced cytotoxicity of doxorubicin against MCF-7/Dox cells. Combination of the two drugs resumed p53 function via inhibiting overexpression of murine doubleminute 2(MDM2) and murine doubleminute 4(MDM4) leading to G2/M arrest and apoptosis in MCF-7/Dox cells. Combination of the two drugs had no effect on P-glycoprotein mRNA expression and P-glycoprotein ATPase activity but increased doxorubicin accumulation in MCF-7/Dox cells. The increased doxorubicin accumulation maybe associate with metabolic stress. Combination of metformin and 2-deoxyglucose initiated a strong metabolic stress in MCF-7/Dox cells via inhibiting glucose uptake, lactate, fatty acid, ATP production and protein kinase B(AKT)/ mammalian target of rapamycin(mTOR) pathway. Taken together, combination of metformin and 2-deoxyglucose reverses MDR of MCF-7/Dox cells by recovering p53 function and increasing doxorubicin accumulation. Furthermore, doxorubicin selectively increases MCF-7/Dox apoptosis via aggravating metabolic stress induced by metformin plus 2-deoxyglucose. The mutually reinforcing effect made the combination of metformin and 2DG had a better effect on reversing MDR.