Background: Acute kidney injury (AKI) is a severe kidney disease. Drug-induced AKI (D-AKI) is one type of AKI, which is difficult to be diagnosed. The incidence of D-AKI in China has rarely been studied. This study aims to explore the disease burden, related drugs and diagnosis status of D-AKI. Methods: A nationwide cross-sectional survey was conducted in adult patients from 23 academic hospitals in 17 provinces in mainland China. Suspected AKI was screened based on serum creatinine changes according to the 2012 Kidney Disease: Improving Global Outcomes (KDIGO) Clinical Practice Guideline for Acute Kidney Injury and patients who met the diagnosis of hospital-acquired AKI in January and July of 2014 were defined. D-AKI was firstly evaluated by pharmacists using Naranjo Adverse Drug Reaction Probability Scale and further confirmed by nephrologists through carefully reviewing the medical records. Findings: Altogether 280,255 hospitalized patients were screened and 1960 cases were diagnosed as hospital-acquired AKI, among which 735 cases were defined as D-AKI (37.50%, 735/1960) with a hospital mortality rate of 13.88% and 54.34% of the survivors not achieving full renal recovery. 1642 drugs were related to AKI in these 735 D-AKI patients. Anti-infectives (34.35%, 564/1642), diuretics (21.80%, 358/1642) and proton pump inhibitors (PPIs) (10.48%, 172/1642) were the top 3 types of drugs relavent to D-AKI, accounting for 66.63% cumulatively. Besides age, AKI staging, severe disease, hypoalbuminemia, plasma substitutes and carbapenems related D-AKI were independent risk factors for in-hospital mortality of D-AKI patients. Interpretation: In China, D-AKI has caused a substantial medical burden. Chinese pharmacists and nephrologists should bear the major responsibility of leading the campaign of managing D-AKI. Funding Statement: This study is supported by Medical Policy and Administration Department, National Health and Family Planning Commission of China, 2015. The National Natural Science Foundation of China (No.91742205 and No.81625004), the Beijing Young Scientist Program (BJJWZYJH01201910001006), and Peking University Clinical Scientist Program by the Fundamental Research Funds for the Central Universities. Declaration of Interests: The authors declare that they have no conflicts of interest.Ethics Approval Statement: This study was approved by the Ethics Committee of Xuanwu Hospital of Capital Medical University.
Objective
To compare the accuracy of Marsh model and Schnider model for propofol target-controlled infusion (TCI) system.
Methods
Eighty patients, aged 20-60 yr, of American Society of Anesthesiologists physical status Ⅰ or Ⅱ, with body mass index of 17.5-28.0 kg/m2, scheduled for elective gynecological operation under general anesthesia, were equally and randomly divided into either Marsh model group (group M) or Schnider model group (group S) using a random number table.The target plasma concentration was set at 3 μg/ml in both groups.During TCI and at different time points after the end of TCI, the blood samples were collected for determination of blood propofol concentrations by high performance liquid chromatography with fluorescence detector.The difference between measured and predicted concentrations (△C) at each time point was calculated.The median performance error (MDPE), median absolute performance error (MDAPE), and wobble of propofol TCI system were calculated in each group.
Results
In M and S groups, the MDPE was 9.90% and 14.00%, respectively; the MDAPE was 11.43% and 14.49%, respectively; the wobble was 7.77% and 7.79%, respectively.There was no significant difference in △C at each time point during TCI between group M and group S (P>0.05). After TCI was stopped, △C at each time point was significantly lower in group M than in group S (P<0.05).
Conclusion
Marsh model provides higher accuracy than Schnider model for propofol TCI system in the patients undergoing gynecological operation.
Key words:
Propofol; Drug delivery systems; Pharmacokinetics
There are several reports describing population pharmacokinetic (PPK) models of valproic acid (VPA). However, little was known in Chinese adult patients with epilepsy. The present study aimed to establish a PPK model for VPA in Chinese adult epileptic patients and to demonstrate its use for dose individualization.Data were obtained from a prospective study of 199 adult epileptic patients at 5 hospitals. The trough concentrations at steady state were measured by fluorescence polarization immunoassay. Data were analyzed using the Nonlinear Mixed Effects Model software. The serum trough concentrations at steady state were also measured using samples (n = 20) collected prospectively from a different hospital from those providing the data for deriving the original model. These independent samples served as an evaluation group.The important determinants of apparent VPA clearance were daily dose, body weight, and combination with carbamazepine, phenytoin, or phenobarbital. The final model predicted the individualized doses accurately. A total of 85% of the trough concentrations in the evaluation group were accurately predicted by the final model, whereas the prediction errors of the other patients were all < ± 31%.A PPK model was developed to estimate the individual clearance for patients taking VPA and could be applied for individualizing doses in the target population.
The study aimed to establish a population pharmacokinetic/pharmacodynamic (PPK/PD) model of warfarin. PCR-RFLP technique was used to genotype the CYP2C9 and VKORC1 polymorphisms of 73 patients. RP-HPLC-UV method was used to determine the 190 plasma concentrations of warfarin. Application of NONMEM, the clinical information and 263 international normalized ratio (INR) monitoring data were used to investigate the effect of genetic, physiological, pathological factors, other medication on clearance and anticoagulant response. The final model of warfarin PPK/PD was described as follows: CL = θCL · (WT/60)θWT · θCYP · eηCL (if CYP2C9*1/*1, θCYP = 1; if *1/*3, θCYP = 0.708); EC50 = θEC50 · θVKOR · eηEC50 (if VKORC1- 1639AA, θVKOR = 1; if GA, θVKOR = 2.01; V = θV; K(E0) = θK(E0); Emax = θEmax; E0 = θE0 · eηE0. Among them, the body weight (WT), CYP2C9 and VKORC1 genotype had conspicuous effect on warfarin PK/PD parameters. The goodness diagnosis, Bootstrap, NPDE verification showed that the final model was stable, effective and predictable. It may provide a reference for opitimizing the dose regimen of warfarin.
A 65-year-old male patient was treated with pyridostigmine bromide tablets (30 mg thrice daily), azathioprine tablets (75 mg twice daily), and prednisone acetate tablets (15 mg once daily) for myasthenia gravis. Two months later, the patient developed abdominal pain, nausea, and vomiting. The laboratory tests showed the blood lipase (LPS) 909 U/L and the urine amylase (AMS) 3 838 U/L. The results of abdominal ultrasonography and imaging examination were consistent with the manifestations of pancreatitis. Above-mentioned drugs were not stopped and the patient was treated according to the conventional treatment regimen of acute pancreatitis. However, the symptoms did not improved significantly. On the 11th day after the onset of the disease, he received subcutaneous infusion of octreotide injection, intravenous infusion of pantoprazole sodium for injection, oral metronidazole, and supportive treatments such as fluid supplement and correction of water electrolyte disorders. The laboratoty tests the next day showed that the patient′s blood LPS was 3 332 U/L and AMS was 139 U/L. The acute pancreatitis was considered to be related to azathioprine tablets. Then the drug was stopped and other treatments were continued. The patient′s symptoms improved quickly. Four days later, LPS was 546 U/L and AMS was 49 U/L.
Key words:
Myasthenia gravis; Azathioprine; Pancreatitis
Objective High on-treatment platelet reactivity (HTPR) has been linked to cardiovascular (CV) events after a percutaneous coronary intervention. There have been some controversies on whether a high maintenance dose (MD) of clopidogrel is effective for HTPR patients. Thus, we carried out a meta-analysis to assess the efficacy and safety of a high MD of clopidogrel in patients with HTPR. Methods Searches of PubMed (from 1966 to May 2014), EMBASE (from 1974 to May 2014), and the Cochrane Library (2 May 2014) were performed. All randomized-controlled trials assessing the efficacy and safety of a high MD of clopidogrel in patients with HTPR were included. Results A total of eight randomized-controlled trials including 3865 patients were included for analysis. In patients with HTPR, high-dose clopidogrel significantly reduced the risk of major adverse CV events or major adverse cardiac and cerebrovascular events [risk ratio (RR) 0.59; 95% confidence interval (CI) 0.39–0.88], stent thrombosis (RR 0.43; 95% CI 0.20–0.92), and target vessel revascularization (RR 0.31; 95% CI 0.10–0.93), without increasing major bleeding (RR 0.75; 95% CI 0.43–1.31) compared with standard-dose clopidogrel. Conclusion A high MD of clopidogrel may be a feasible and readily available treatment to lower the risk of recurrent CV events in patients with HTPR after undergoing percutaneous coronary intervention, especially in HTPR patients with coronary artery disease and chronic kidney disease.
'/%3e%3cuse xlink:href='%23a' transform='rotate(23.036 .093 25.536)'/%3e%3cuse xlink:href='%23a' transform='rotate(45.87 1.273 16.18)'/%3e%3cuse xlink:href='%23a' transform='rotate(69.945 .996 12.078)'/%3e%3cuse xlink:href='%23a' transform='rotate(20.66 -19.689 31.932)'/%3e%3c/svg%3e)