Study on population pharmacokinetics of dabigatran in elderly patients with non-valvular atrial fibrillation / 中国药房

OBJECTIVE To analyze influential factors for dabigatran exposure in elderly patients with non-valvular atrial fibrillation. METHODS The clinical information of 75 elderly patients diagnosed with non-valvular atrial fibrillation was collected from our hospital in Jan. 2019-Jun. 2020. One or two steady-state blood drug concentration samples were collected from each patient. NONMEM 7.2.0 software was used to establish a population pharmacokinetics model of dabigatran； the effects of different covariates on the apparent clearance of dabigatran were investigated， and the final model was verified by goodness of fit and Bootstrap method； NONMEM 7.2.0 software was used to analyze the drug exposure of ordinary elderly patients and elderly patients after taking dabigatran ester in different disease states. RESULTS Totally 122 blood concentration samples of dabigatran were collected. Advanced age， creatinine clearance and history of chronic heart failure were screened out as three significant covariates that influenced the clearance of dabigatran in elderly patients. The exposure of population with advanced age increased by about 50% compared with the general elderly， the exposure of population with history of chronic heart failure increased by nearly 30% compared with population without， and the exposure of population with moderate and severe renal injury increased by about 30% and 80% compared with mild. CONCLUSIONS Advanced age， renal injury and history of chronic heart failure are influential factors for elevated systemic exposure of dabigatran.

Study on environmental residues detection and cleaning method of 15 cytotoxic antineoplastic drugs in PIVAS of our hospital / 中国药房

OBJECTIVE To provide a method to reduce environmental residues for pharmacy intravenous admixture service （PIVAS）， and ensure the occupational health of medical staff. METHODS The residues of 15 cytotoxic antineoplastic drugs such as gemcitabine were detected by UPLC-Q-Orbitrap-HRMS. The cleaning process was optimized with the residual quantity as the index. Nitrogen blowing method was used for alcohol volatilization experiment. CCK-8 assay was used to detect the effect of chlorine-containing disinfectant on the toxicity of cytotoxic antitumor drugs. RESULTS The linear range of 15 cytotoxic antineoplastic drugs such as gemcitabine were 0.5-1 000 ng/mL. RSDs of intra-day and intra-day precision were no higher than 20.00%. Six drugs including gemcitabine， isocyclophosphamide and cyclophosphamide were detected in the PIVAS environment of our hospital， and the residue of cyclophosphamide was relatively high. The optimal cleaning procedure was cleaning once with water + cleaning once with 1 000 mg/L chlorine-containing disinfectant + cleaning once with 75% alcohol， wiping with dry gauze method. The results of alcohol volatilization test showed that there was no significant difference in drug residues between control group and 75% alcohol group （P＞0.05）. The results of CCK-8 test showed that compared with control group， the survival rates of the cells treated with 15 cytotoxic antineoplastic drugs were decreased significantly （P＜0.01）； the survival rates of the cells treated with 15 cytotoxic antineoplastic drugs+chlorine-containing disinfectant were significantly higher than those treated with 15 cytotoxic antineoplastic drugs （P＜0.01）. CONCLUSIONS A method for the simultaneous determination for residues of 15 cytotoxic antineoplastic drugs such as gemcitabine in PIVAS is successfully established； the optimal cleaning procedure can significantly reduce the residues of drugs， the use of chlorine- containing disinfectant can significantly reduce the toxicity of drug， and the residual drugs will not cause secondary contamination of the operating area with alcohol volatilization.

Minimizing VPD Fluctuations Maintains Higher Stomatal Conductance and Photosynthesis, Resulting in Improvement of Plant Growth in Lettuce.

Vapor pressure deficit (VPD) is considered to be one of the major environmental factors influencing stomatal functions and photosynthesis, as well as plant growth in crop and horticultural plants. In the greenhouse cultivation, air temperature and relative air humidity are regulated by switching on/off the evaporative systems and opening/closing the roof windows, which causes VPD fluctuation. However, it remains unclear how VPD fluctuation affects photosynthetic and growth performance in plants. Here, we examined the effects of the VPD fluctuation on the photosynthetic and growth characteristics in lettuce (Lactuca sativa L.). The parameters for gas exchange and chlorophyll fluorescence and biomass production were evaluated under the conditions of drastic (1.63 kPa for 6 min and 0.63 for 3 min) or moderate (1.32 kPa for 7 min and 0.86 kPa for 3 min) VPD fluctuation. The drastic VPD fluctuation induced gradual decrease in stomatal conductance and thus CO2 assimilation rate during the measurements, while moderate VPD fluctuation caused no reduction of these parameters. Furthermore, data showed moderate VPD fluctuation maintained leaf expansion and the efficiency of CO2 diffusion across leaf surface, resulting in enhanced plant growth compared with drastic VPD fluctuation. Taken together, fine regulation of VPD can be crucial for better plant growth by maintaining the photosynthetic performance in lettuce. The present work demonstrates the importance of VPD control during plant cultivation in plant factories and greenhouses.