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Objectives: Linezolid is a commonly used antibiotic in the clinical treatment of gram-positive bacterial infections. The impacts of drug interactions on the pharmacokinetics of linezolid are often overlooked. This manuscript aims to review the medications that affect the pharmacokinetics of linezolid. Methods: In accordance with Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines, we queried the PubMed, Embase, and Cochrane Library for publications from database establishment to November 3, 2023, using the search terms: "Linezolid" and "interaction," or "interact," or "drug-drug interaction," or "co-treatment," or "cotreatment," or "combined," or "combination." Results: A total of 24 articles were included. Among the reported medication interactions, rifampicin, levothyroxine, venlafaxine, and phenobarbital could reduce the concentration of linezolid; clarithromycin, digoxin, cyclosporine, proton pump inhibitors, and amiodarone could increase the concentration of linezolid, while aztreonam, phenylpropanolamine, dextromethorphan, antioxidant vitamins, and magnesium-containing antacids had no significant effects on linezolid pharmacokinetics. The ratio of mean (ROM) of linezolid AUC in co-treatment with rifampicin to monotherapy was 0.67 (95%CI 0.58–0.77) and 0.63 (95%CI 0.43–0.91), respectively, in 2 studies, and co-treatment with 500 mg clarithromycin to monotherapy was 1.81 (95%CI 1.49–2.13). Conclusions: This systematic review found that numerous drugs have an impact on the pharmacokinetics of linezolid, and the purported main mechanism may be that linezolid is the substrate of P-glycoprotein. In clinical practice, it is prudent to pay attention to the changes in linezolid pharmacokinetics caused by interactions. Conducting therapeutic drug monitoring (TDM) is beneficial to improve efficacy and reduce adverse reactions of linezolid. [ABSTRACT FROM AUTHOR]

Aims. The aim of this study is to assess the relationship between rivaroxaban plasma concentration quantified by the gold standard and anticoagulant activities measured by routine coagulation assays in Chinese atrial fibrillation (AF) patients. Whether the normal results of these tests were reliable to rule out clinically relevant rivaroxaban levels at various thresholds was also explored. The effect of clinical drug-drug interactions (DDIs) on the exposure and anticoagulant effect of rivaroxaban were further evaluated. Methods. 116 patients receiving rivaroxaban for the management of nonvalvular AF were recruited. Rivaroxaban concentrations and coagulation tests were measured by ultra-performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS) and a blood coagulation analyzer, respectively. Results. The correlation of trough concentration (Ctrough) and prothrombin time (PT) or international normalized ratio (INR) was moderate with Spearman's correlation coefficient of 0.495 and 0.506, respectively. A normal PT/INR was unable to rule out Ctrough levels of >30 ng/mL and >50 ng/mL, but the negative predictive value reached 100% to exclude Ctrough of >100 ng/mL. Ctrough showed a small correlation with activated partial thromboplastin time (aPTT) (Spearman's correlation coefficient: 0.241) and no correlation with thrombin time (TT) (Spearman's correlation coefficient: 0.074). Neither aPTT nor TT accurately predicted Ctrough at any concentration. Peak concentration (Cpeak) did not correlate with any coagulation parameters. The presence of digoxin and febuxostat significantly increased rivaroxaban Ctrough by 2.18 fold and prolonged PT and INR by 44.16% and 43.60%, respectively. Conclusions. Normal routine coagulation assays were insufficient to monitor therapy with rivaroxaban. Poor correlations between rivaroxaban concentration and routine coagulation assays were observed in Chinese AF patients. The use of digoxin/febuxostat alone had no effect on rivaroxaban concentrations; however, combined strong breast cancer resistance protein inhibitor (febuxostat) and P-glycoprotein probe (digoxin) in patients with renal impairment is likely to cause clinically significant DDI with rivaroxaban. More studies are needed to establish routine therapeutic drug monitoring of rivaroxaban in clinical practice. [ABSTRACT FROM AUTHOR]

Aims: Prior studies have reported conflicting results on digoxin's impact on clinical outcomes and quality of life, and there are limited data from Asia. The aim of this study is to evaluate the use of digoxin and its impact on clinical outcomes and quality of life in a high-risk cohort of elderly Chinese atrial fibrillation (AF) patients.Methods and Results: The Optimal Thromboprophylaxis in Elderly Chinese Patients with Atrial Fibrillation (ChiOTEAF) registry is a prospective, multicentre nationwide study conducted from October 2014 to December 2018. Endpoints of interest were the composite outcome of all-cause death/any thromboembolism (TE), all-cause death, cardiovascular death, sudden cardiac death, and TE events, as well as the quality of life. The eligible cohort for this analysis included 6391 individuals, of whom 751 (11.8%) patients were treated with digoxin. On multivariate analysis, the use of digoxin was associated with a higher odds ratio (OR) of composite outcome [OR: 1.71; 95% confidence interval (CI): 1.32-2.22], all-cause death (OR: 1.62; 95% CI: 1.23-2.14), and any TE (OR: 1.78; 95% CI: 1.08-2.95). Results were consistent in a subgroup of patients with diagnosed heart failure (HF) and patients with permanent AF. The use of digoxin was associated with worse health-related quality of life (mean EQ index: 0.76 ± 0.19 vs. 0.84 ± 0.18; P < 0.001).Conclusions: In this nationwide cohort study, digoxin use was associated with an overall higher risk of the composite outcome of all-cause death/any TE, all-cause death, and any TE, regardless of HF diagnosis. Patients treated with digoxin had a worse health-related quality of life. [ABSTRACT FROM AUTHOR]

Purpose: Pregnancy increases stress on the circulation of parturient with mitral stenosis secondary to rheumatic heart disease and increases the risk of peripartum heart failure, especially during delivery. This study investigated the epidural anesthesia management for cesarean section in pregnant women with rheumatic heart disease and mitral stenosis.Methods: 48 parturients with rheumatic heart disease and mitral stenosis that had cesarean section deliveries with epidural anesthesia in the Union Hospital, Fujian Medical University (Fuzhou, China) from Jan 2002 to Dec 2012 were retrospectively analyzed. Heart rate (HR), systolic arterial pressure (SAP), diastolic arterial pressure (DAP), mean arterial pressure (MAP), central venous pressure (CVP), fluid intake volume and fluid output volume (blood loss + urine volume) were analyzed.Results: Medication included digitalis drugs for heart failure or potential heart failure, digoxin and furosemide for chronic congestive heart failure and beta blockers for arrhythmia. Frequent premature ventricular contractions were treated with lidocaine and propafenone. Dexamethasone was administered when heart failure occurred during less than 37 weeks gestation. HR, SAP, DAP, MAP and CVP were significantly increased at the time of delivery. The fluid intake volume was more elevated in the NYHA III-IV group of parturients than the NYHA I-II group, while fluid output volume was less. All parturients survived.Conclusions: Epidural anesthesia was applied successfully for cesarean sections for parturients with rheumatic heart disease and mitral stenosis. [ABSTRACT FROM AUTHOR]

Background: Hepatocellular carcinoma (HCC) is a common and aggressive cancer, and the treatment options are limited for patients with advanced HCC. Bufalin, the major digoxin-like component of the traditional Chinese medicine Chansu, exhibits significant anti-tumor activities in many tumor cell lines. In the present study, we investigated the effect of bufalin on the inhibition of an AKT-related signaling pathway, and examined the relationship between regulatory proteins and anti-tumor effects in hepatoma cells. Methods: Proliferation, wound healing, transwell-migration/invasion and adhesion assays were performed in HCCLM3 and HepG2 cell lines. The protein levels of pAKT, AKT, pGSK3β, GSK3β, pβ-catenin, β-catenin, E-cadherin, MMP-9, and MMP-2 were measured by western blot analysis. E-Cadherin and β-catenin expression levels were also evaluated by immunofluorescence. Results: Bufalin inhibited hepatoma cell proliferation, migration, invasion and adhesion. In addition, treatment with bufalin significantly decreased the levels of pAKT, pGSK3β, MMP-9, and MMP-2, while increasing the levels of GSK3β and E-cadherin and suppressing the nuclear translocation of β-catenin. Conclusions: Bufalin is a potential anti-HCC therapeutic candidate through its inhibition of the AKT/GSK3β/β-catenin/ E-cadherin signaling pathway. Further studies with bufalin are warranted in patients with HCC, especially those with the disease at advanced stages. [ABSTRACT FROM AUTHOR]

Aims: Prior studies have reported conflicting results on digoxin's impact on clinical outcomes and quality of life, and there are limited data from Asia. The aim of this study is to evaluate the use of digoxin and its impact on clinical outcomes and quality of life in a high-risk cohort of elderly Chinese atrial fibrillation (AF) patients., Methods and Results: The Optimal Thromboprophylaxis in Elderly Chinese Patients with Atrial Fibrillation (ChiOTEAF) registry is a prospective, multicentre nationwide study conducted from October 2014 to December 2018. Endpoints of interest were the composite outcome of all-cause death/any thromboembolism (TE), all-cause death, cardiovascular death, sudden cardiac death, and TE events, as well as the quality of life. The eligible cohort for this analysis included 6391 individuals, of whom 751 (11.8%) patients were treated with digoxin. On multivariate analysis, the use of digoxin was associated with a higher odds ratio (OR) of composite outcome [OR: 1.71; 95% confidence interval (CI): 1.32-2.22], all-cause death (OR: 1.62; 95% CI: 1.23-2.14), and any TE (OR: 1.78; 95% CI: 1.08-2.95). Results were consistent in a subgroup of patients with diagnosed heart failure (HF) and patients with permanent AF. The use of digoxin was associated with worse health-related quality of life (mean EQ index: 0.76 ± 0.19 vs. 0.84 ± 0.18; P < 0.001)., Conclusions: In this nationwide cohort study, digoxin use was associated with an overall higher risk of the composite outcome of all-cause death/any TE, all-cause death, and any TE, regardless of HF diagnosis. Patients treated with digoxin had a worse health-related quality of life., (Published on behalf of the European Society of Cardiology. All rights reserved. © The Author(s) 2022. For permissions, please email: journals.permissions@oup.com.)

The primary objectives of this study were to investigate the suitability of a 6-probe cocktail (caffeine, tolbutamide, omeprazole, dextromethorphan, midazolam, and digoxin) to be used as a tool for assessing the activity of drug metabolizing enzymes and transporters, and examine differences in the way drugs are handled among groups with different genetic regulation of these processes. This was a single-center, open-label, phase I clinical study involving 20 young, healthy Chinese volunteers (equal gender distribution). The subjects were administered a single, oral dose of the 6-probe cocktail and serum samples were collected to assess the disposition of the different probe substrates and produced metabolites. The serum samples were analyzed using ultra-performance liquid chromatography-electrospray ionization-tandem mass spectrometry technology. The DNA samples were subjected to whole exome sequencing. Nineteen healthy volunteers completed the study. The 6-probe cocktail was safe and well-tolerated by all the subjects. The parent substrates and metabolites-caffeine (paraxanthine), dextromethorphan (dextrorphan), digoxin, midazolam (1-hydroxy-midazolam), omeprazole (5-hydroxy-omeprazole), and tolbutamide (4-hydroxy-tolbutamide)-were within the detectable window. Genetic variations known to alter drug metabolism (CYP2D6*10, CYP2C19*2, CYP2C19*3, and CYP2C9*3) were identified and generally correlated with phenotypic status. The 6-probe cocktail appeared to be suitable for assessing drug metabolizing activities. This, in conjunction with individual genetics, will pave the way for the implementation of personalized medicine in clinical practice. This will hopefully improve efficacy and reduce the incidence of adverse drug reactions., (© 2022. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

AbstractAim:To establish a population pharmacokinetic (PPK) model of digoxin in older Chinese patients to provide a reference for individual medication in clinical practice.Methods:Serum concentrations of digoxin and clinically related data including gender, age, weight (WT), serum creatinine (Cr), alanine aminotransferase (ALT), aspartate aminotransferase (AST), blood urea nitrogen (BUN), albumin (ALB), and co-administration were retrospectively collected from 119 older patients taking digoxin orally for more than 7 d. NONMEM software was used to get PPK parameter values, to set up a final model, and to assess the models in clinical practice.Results:Spironolactone (SPI), WT, and Cr markedly affected the clearance rate of digoxin. The final model formula is Cl/F=5.9×[1–0.412×SPI;[times;[1–0.0101×(WT–62.9);[times;[1–0.0012×(Cr–126.8)] (L/h); Ka=1.63 (h−1); Vd/F=550 (L). The population estimates for Cl/F and Vd/F were 5.9 L/h and 550 L, respectively. The interindividual variabilities (CV) were 49.0% for Cl/F and 94.3% for Vd/F. The residual variability (SD) between observed and predicted concentrations was 0.365 μg/L. The difference between the objective function value and the primitive function value was less than 3.84 (P>0.05) by intra-validation. Clinical applications indicated that the percent of difference between the predicted concentrations estimated by the PPK final model and the observed concentrations were −4.3%–+25%. Correlation analysis displayed that there was a linear correlation between observated and predicted values (y=1.35x+0.39, r=0.9639, P<0.0001).Conclusion:The PPK final model of digoxin in older Chinese patients can be established using the NONMEM software, which can be applied in clinical practice. [ABSTRACT FROM AUTHOR]

This is the first study to investigate vertical transmission of Chlamydia trachomatis in Chongqing China. For this study, 300 cervical swab samples from pregnant women and 305 nasopharygeal swab samples from their babies (605 specimens) were collected for nest polymerase chain reaction (nPCR) of the ompl gene , which encodes the major outer membrane protein (MOMP) and typed C. trachomatis using Cleavase fragment-length polymorphism (CFLP) labeled with digoxin. From these samples, 11% (33/300) of pregnant women samples were successfully amplified. The vertical transmission rate of C. trachomatis from mother to baby was 24% (8/33). The vertical transmission rates were 66.7% (6/9) for mothers with vaginal delivery and 8.3% (2/24) for those with cesarean section. The incidence of premature membrane rupture among C. trachomatis-positive pregnant women was 30.3% (10/33), which was greater than among those who were C. trachomatis-negative (13.5%, 36/267; χ2 = 4.2; p < 0.05). Four genotypes including type E (3 pairs), type F (2 pairs), type H (2 pairs), and type D (1 pair) were observed by CFLP assay labeled with digoxin and confirmed by DNA sequencing in the 16 C. trachomatis-positive samples from eight pregnant women and their eight infants. Each pair of matched maternal–infantile samples showed identical CFLP. This study showed the incidence of C. trachomatis infection in pregnant women, the vertical transmission rate for C. trachomatis, and the genotypes of C. trachomatis in Chongqing, China. The CFLP assay labeled at the 5′ end of the forward primer with digoxin was first used successfully to genotype of C. trachomatis. As a promising method for C. trachomatis genotyping, CFLP had good sensitivity, reproducibility, and simplicity and no radioactive contamination. [ABSTRACT FROM AUTHOR]

Background: Chan Su, a traditional Chinese medicine, is used for treating the heart diseases and other systemic illnesses. Our studies with animal model have revealed its role in increasing intracellular calcium concentration in cardiomyocytes. Nitric oxide (NO), a second messenger molecule, and its metabolites have been demonstrated to maintain and modulate multiple physiologic functions including the cardiovascular and reproductive systems. In order to explore the mechanism of action of Chan Su, we studied the ability of Chan Su to stimulate NO production in cultured trophoblastic BeWo cells. Materials and methods: BeWo cell is a cloned established cell line purified from human choriocarcinoma. These cells have some similarities in biological behavior with endothelial cells. Therefore, BeWo cell line may act as a model system for production of nitric oxide by Chan Su both in placenta and in cardiovascular tissue, and the results can easily be extrapolated to cardiomyocytes. Very small amount of ethanol extract of Chan Su was added to the cultured cells in KBM buffer and a chemiluminescence system was used for the measurement of nitric oxide. The amounts of Chan Su extract added to cultured cells were comparable to expected level of Chan Su in human serum after ingestion. We also repeated these experiments with bufalin, the active component of Chan Su. Results: The ethanol extract of Chan Su (5 and 10 μg/ml) significantly increased NO production up to 110% of basal control value, but higher concentrations (40 and 80 μg/ml) of Chan Su (as expected in an overdose) resulted in decreased NO production below the control level. This biphasic effect on nitric oxide production was also observed with bufalin, the active component of Chan Su responsible for its digoxin-like immunoreactivity. The presence of bufalin in Chan Su preparation was confirmed by thin layer chromatography (TLC) analysis. Conclusions: Chan Su as well as bufalin is able to modulate the production of NO in BeWo cell line. [Copyright &y& Elsevier]

Aims: The aim of this study was to investigate the impact of digoxin use on the outcomes of patients with heart failure with reduced ejection fraction (HFrEF) and its possible interaction with atrial fibrillation or use of currently guideline-recommended treatments in the real world in China., Methods and Results: Patients hospitalized with HFrEF from 45 hospitals participating in the China National Heart Failure Registration Study (CN-HF) were enrolled to assess the all-cause mortality, HF mortality, all-cause re-hospitalization, and HF re-hospitalization associated with digoxin use. Eight hundred eighty-two eligible HFrEF patients in the CN-HF registry were included: 372 patients with digoxin and 510 patients without digoxin. Among them, 794 (90.0%) patients were followed up for the endpoint events, with a median follow-up of 28.6 months. Kaplan-Meier survival analysis showed that the all-cause mortality (P < 0.001) and all-cause re-hospitalization (P = 0.020) were significantly higher in digoxin group than non-digoxin group, while HF mortality (P = 0.232) and HF re-hospitalization (P = 0.098) were similar between the two groups. The adjusted Cox proportional-hazards regression analysis demonstrated that digoxin use remained as an independent risk factor for increased all-cause mortality [hazard ratio (HR) 1.76; 95% confidence interval (CI) 1.27-2.44; P = 0.001] and all-cause re-hospitalization (HR 1.27; 95% CI 1.03-1.57; P = 0.029) in HFrEF patients and the predictive value of digoxin for all-cause mortality irrespective of rhythm or in combination with other guideline-recommended therapies., Conclusions: Digoxin use is independently associated with increased risk of all-cause mortality and all-cause re-hospitalization in HFrEF patients., (© 2020 The Authors. ESC Heart Failure published by John Wiley & Sons Ltd on behalf of European Society of Cardiology.)

Aim: The dose of digoxin is often difficult to be determined precisely. The aim of this study was to retrospectively investigate the effect of blood biochemical indexes on the serum concentration of digoxin. Materials & methods: We collected the data of hospitalized patients treated orally with digoxin in Nanjing Drum Tower Hospital (Nanjing, China) from 2016 to 2018. Descriptive statistics was used to analyze the patients' comprehensive condition. Results: A total of 425 patients were included in the study. Through analysis, nine factors were included in the regression model of the serum concentration of digoxin, and this regression model showed good predictive performance (r 2  = 0.83138; p < 0.001). Conclusion: The regression model for the prediction of serum concentration of digoxin has clinical significance, and can provide research basis for individualized medication of digoxin.

This is the first study to investigate vertical transmission of Chlamydia trachomatis in Chongqing China. For this study, 300 cervical swab samples from pregnant women and 305 nasopharygeal swab samples from their babies (605 specimens) were collected for nest polymerase chain reaction (nPCR) of the ompl gene, which encodes the major outer membrane protein (MOMP) and typed C. trachomatis using Cleavase fragment-length polymorphism (CFLP) labeled with digoxin. From these samples, 11% (33/300) of pregnant women samples were successfully amplified. The vertical transmission rate of C. trachomatis from mother to baby was 24% (8/33). The vertical transmission rates were 66.7% (6/9) for mothers with vaginal delivery and 8.3% (2/24) for those with cesarean section. The incidence of premature membrane rupture among C. trachomatis-positive pregnant women was 30.3% (10/33), which was greater than among those who were C. trachomatis-negative (13.5%, 36/267; chi(2) = 4.2; p < 0.05). Four genotypes including type E (3 pairs), type F (2 pairs), type H (2 pairs), and type D (1 pair) were observed by CFLP assay labeled with digoxin and confirmed by DNA sequencing in the 16 C. trachomatis-positive samples from eight pregnant women and their eight infants. Each pair of matched maternal-infantile samples showed identical CFLP. This study showed the incidence of C. trachomatis infection in pregnant women, the vertical transmission rate for C. trachomatis, and the genotypes of C. trachomatis in Chongqing, China. The CFLP assay labeled at the 5' end of the forward primer with digoxin was first used successfully to genotype of C. trachomatis. As a promising method for C. trachomatis genotyping, CFLP had good sensitivity, reproducibility, and simplicity and no radioactive contamination.