Linezolid is the first synthetic oxazolidone agent to treat infections caused by Gram-positive pathogens. Infected patients with liver dysfunction (LD) are more likely to suffer from adverse reactions, such as thrombocytopenia, when standard-dose linezolid is used than patients with LD who did not use linezolid. Currently, pharmacokinetics data of linezolid in patients with LD are limited. This study aimed to characterize pharmacokinetics parameters of linezolid in patients with LD, identify the factors influencing the pharmacokinetics, and propose an optimal dosage regimen. We conducted a prospective study and established a population pharmacokinetics model with the Phoenix NLME software. The final model was evaluated by goodness-of-fit plots, bootstrap analysis, and prediction corrected-visual predictive check. A total of 163 concentration samples from 45 patients with LD were adequately described by a one-compartment model with first-order elimination along with prothrombin activity (PTA) and creatinine clearance as significant covariates. Linezolid clearance (CL) was 2.68 liters/h (95% confidence interval [CI], 2.34 to 3.03 liters/h); the volume of distribution (V) was 58.34 liters (95% CI, 48.00 to 68.68 liters). Model-based simulation indicated that the conventional dose was at risk for overexposure in patients with LD or severe renal dysfunction; reduced dosage (300 mg/12 h) would be appropriate to achieve safe (minimum steady-state concentration [Cmin,ss] at 2 to 8 μg/ml) and effective targets (the ratio of area under the concentration-time curve from 0 to 24 h [AUC0–24] at steady state to MIC, 80 to 100). In addition, for patients with severe LD (PTA, ≤20%), the dosage (400 mg/24 h) was sufficient at an MIC of ≤2 μg/ml. This study recommended therapeutic drug monitoring for patients with LD. (This study has been registered in the Chinese Clinical Trial Registry under no. ChiCTR1900022118.)
Purpose: To compare the bioequivalence of two formulations of valsartan (80 mg capsules) under fasting and fed conditions in healthy Chinese volunteers using a full-replicate study design. Methods: A total of 78 Subjects were randomly assigned to fasting cohort (n = 48) or fed cohort (n = 30). Each cohort includes 4 single-dose observation periods and 3-day washout periods. Blood samples were collected at designed time point. Plasma concentration of valsartan was analyzed by a validated LC-MS/MS method. Noncompartmental analysis method was employed to determine the pharmacokinetic parameters. Based on the withinsubject standard deviation (S WR) of the reference formulation, either reference-scaled average bioequivalence (RSABE) or average bioequivalence (ABE) method was used to evaluate the bioequivalence of the two formulations. Results: Under fasting conditions, the RSABE method was used to evaluate the bioequivalence of C max (S WR >0.294), while ABE method was used to evaluate the bioequivalence of AUC 0-t and AUC 0-∞. The geometric mean ratio (GMR) of the test/reference for C max was 99.52%, and the 95% upper confidence bound was <0. For AUC 0-t and AUC 0-∞ comparisons, GMRs were 102.07% and 101.92%, and the 90% CIs of the test/reference were 96.28%-108.21%, 96.28%-107.88%, respectively. Under fed conditions, the S WR value of C max , AUC 0-t and AUC 0-∞ all exceeded the cutoff value of 0.294 and therefore, the RSABE method was used. The GMRs for C max , AUC 0-t and AUC 0-∞ were 98.78%, 103.33% and 103.08%, respectively, while the 95% upper confidence bound values were all <0. These results all met the bioequivalence criteria for highly variable drugs. All adverse events were mild and transient. Conclusion: In this study, the generic formulation of valsartan 80 mg capsule was considered to be bioequivalent to the reference product under both fasting and fed conditions, and satisfied the requirements for marketing in China. NMPA Registration No: CTR20181422.
Objectives: To investigate the incidence, pathogenesis, as well as mortality rate and causes of end-stage renal disease patients with hemodialysis (ESRD-HD) in Sichuan province of China. Methods: In this retrospective descriptive study, all the data were exported from the Chinese National Renal Data System (CNRDS). The demographic and pathogenic information from 01 January 2011 to 31 December 2016 were statistically analyzed. Results: According to the data from CNRDS, the incidence of ESRD-HD was high in Sichuan province. From 2011 to 2016, the annual incidence rate of ESRD-HD was 61.84, 73.75, 78.04, 66.04, 72.61, and 60.98 per million population (pmp). Male ESRD-HD patients were higher than female patients (1.5:1). The major causes of ESRD-HD in Sichuan province from 2011 to 2016 were chronic glomerulonephritis and diabetic nephropathy. The annual mortality rate of ESRD-HD was 113.20, 91.25, 73.02, 68.56, 68.57, and 58.39 per 1000 person-years. The descending rate of mortality was parallel in both males and females. The mortality rate was observed to be higher in the elderly group (age ≥ 60). The major cause of mortality was cardiovascular diseases (24.48%). Conclusions: In Sichuan province, the incidence of ESRD-HD annually was gradually descending. The elderly and male patients had higher incidence of ESRD-HD. The annual mortality rate of ESRD-HD was declining year by year, and elderly patients aged ≥ 60 contributed to the highest mortality rates. The major cause of death was cardiovascular diseases. This could contribute to a better understanding of ESRD-HD in southwest of China, thus providing better treatment for ESRD in the future.
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