[Efficacy of sacubitril/valsartan in peritoneal dialysis patients with HFpEF and its effect on residual renal function].

Objective: To investigate the efficacy of sacubitril/valsartan in peritoneal dialysis (PD) patients with heart failure with preserved ejection fraction (HFpEF) and its effect on residual renal function. Methods: PD patients with HFpEF in Ningbo First Hospital from March 2018 to August 2021 were retrospectively enrolled and divided into study group with sacubitril/valsartan and control group with valsartan. The clinical baseline data before treatment and clinical indicators during follow-up (6 and 12 months after treatment) were collected and compared between the two groups, and the adverse reactions were also recorded. Results: A total of 99 patients were included in the study. There were 61 patients in the study group, including 44 males and 17 females, with a mean age of (52±13) years. Meanwhile, there were 38 patients in the control group, including 23 males and 15 females, with a mean age of (57±14) years. There was no statistically significant difference in clinical baseline data between the two groups (e.g., age, sex, body mass index, duration of dialysis) (all P>0.05). The N-terminal pro-B-type natriuretic peptide (NT-proBNP) and left ventricular end-systolic dimension (LVDs) were lower, but the left ventricular ejection fraction (LVEF) was higher in the study group than those in the control group at 6 and 12 months after treatment (all P<0.05). The systolic blood pressure (SBP) and diastolic blood pressure (DBP) of the two groups were lower than baseline values at 6 and 12 months after treatment respectively, with statistically significant differences (all P<0.05). However, there were no statistically significant differences in the decreases of SBP and DBP between the two groups at 6 and 12 months after treatment (all P>0.05). The decrease extents in residual estimated glomerular filtration rate (eGFR) [0.52 (-0.05, 1.19) vs 1.72 (0.97, 2.39) ml·min-1·(1.73 m2)-1, P<0.001]and 24-h residual urine volume [200 (-100, 300) vs 300 (137, 400) ml, P=0.018] at 12 months after treatment were lower in the study group than those in the control group. During the follow-up period, hyperkalemia occurred in 16 cases (26.2%) and 13 cases (34.2%) in the study group and the control group, and hypotension occurred in 3 cases (4.9%) and 1 case (2.6%) in the study group and the control group, respectively. There were no adverse reactions such as cough and angioneurotic edema in the two groups. Conclusions: Sacubitril/valsartan can safely and effectively improve cardiac function and lower blood pressure in PD patients with HFpEF. Compared with valsartan, sacubitril/valsartan may be more beneficial to delay the loss of residual renal function in PD patients with HFpEF.

Time resolved absolute extreme ultraviolet radiation measurement on the ENN XuanLong-50 spherical tokamak.

A plasma radiation measurement system for a wide spectral range, based on compact Absolute eXtreme UltraViolet (AXUV) silicon photodiodes, has been implemented on the newly constructed ENN XuanLong-50 (EXL-50) spherical tokamak. The system consists of two 16-channel AXUV16ELG arrays and one AXUV63HS1 single-cell detector mounted on ceramic sockets. The two arrays, facing toward the EXL-50 slim central post from two locations inside a top and a side ConFlat 400 port, have 32 view chords covering the interested plasma region in a poloidal cross section at toroidal 330°. The single-cell detector, seated on a retractable feedthrough, could be arranged flexibly with the help of an ultra-high vacuum compatible gate valve. The design details together with considerations on the EXL-50 specific engineering realities and physics requirements are described. Preliminary results from the EXL-50 2020 experimental campaign are presented.

Toroidal soft x-ray array on the EXL-50 spherical tokamak.

A toroidal soft x-ray array system for spectrum and intensity measurements on the EXL-50 spherical tokamak is described. Silicon drift detectors and digital multichannel analyzers are adopted for all 21 channels of the array, and an average energy resolution of 147 eV at 5.89 keV has been achieved at count rates over 500 kcps. In total, 20 channels of the array are symmetrically observed in both co- and counter-current directions on the EXL-50 mid-plane with a spatial resolution of around 10 cm, and the remaining one serves as a background reference channel. Tungsten emissions from tungsten coating of the limiters on the central post are observed. The influence of hard x rays on measured soft x-ray spectra and system operation is discussed.

Tangential hard x-ray diagnostic array on the EXL-50 spherical tokamak.

A tangential hard x-ray (HXR) diagnostic on the newly constructed ENN XuanLong-50 (EXL-50) spherical tokamak for fast electron emission studies is presented. The HXR detection system consists of a symmetrical CdZnTe semiconductor detector array with a spectral sensitivity range of 20-300 keV. 25 channels have been designed on the 270° horizontal vacuum port with 12 sight lines to observe the forward emission, 12 sight lines to observe the backward emission of fast electrons, and 1 for viewing the central. Currently, ten channels have been in operation in the EXL-50 experiments. The systems are designed to measure the x-ray spectra for the estimation of fast electron temperature and electron velocity distribution in the EXL-50 experiment, which will be useful for understanding the dynamics of fast electrons generated by electron cyclotron resonance heating, for plasma instability and transport studies and for the analysis of plasma heating efficiency.

Demographic and clinical factors associated with immune reconstitution in HIV/HBV co-infected and HIV mono-infected patients: a retrospective cohort study.

OBJECTIVES: To describe the clinical characteristics and factors associated with CD4 T-cell count and CD4/CD8 ratio restoration in HIV mono-infected and HIV/HBV co-infected individuals, and to explore liver and renal functional changes in both groups. METHODS: A retrospective cohort study was performed including 356 HIV/HBV co-infected and 716 HIV mono-infected participants who initiated antiretroviral therapy (ART) during 2013-2017 in Beijing Youan Hospital, China. Demographic and clinical characteristics were compared between the two groups, using χ2 and Mann-Whitney non-parametric tests. Bivariate and multivariate Cox regression models were used to test their association. RESULTS: Baseline HIV viral load and ART regimen were found to be significantly associated with CD4 T-cell restoration among HIV-infected participants, whereas baseline HIV viral load was the only significant factor associated with CD4 T-cell restoration in HIV/HBV co-infected participants. The final model showed that baseline HIV viral load and ART regimen were significantly associated with CD4/CD8 ratio restoration among HIV-infected participants, while baseline HIV viral load was the significant factor. Liver and renal functions were similar at the endpoint (P > 0.05). CONCLUSIONS: Baseline HIV viral load count was found to be the key factor affecting immune restoration in both HIV and HIV/HBV individuals. Future multi-wave prospective studies are needed to clarify the potential biological mechanism.

[Carcinogenicity study of CD133(+)CD44(+) laryngeal cancer stem cells and identification of related microRNAs].

Objective: To compare the carcinogenic abilities of CD133(+)CD44(+) laryngeal cancer stem cells and general laryngeal cancer stem cells and to identify the mechanism underlying the action of miRNAs. Methods: Solid tumor-derived laryngeal carcinoma stem cells and Hep-2-derived laryngeal carcinoma stem cells were cultured, and CD133(+)CD44(+) laryngeal cancer stem cells were sorted by flow cytometry. Boden chamber invasion assay, cell migration assay and tumor formation assay were then performed to compare the invasion, migration and tumorigenic abilities of CD133(+)CD44(+) laryngeal cancer stem cells and general laryngeal cancer stem cells. And then, miRNAs isolated from two laryngeal cancer stem cells were detected and analysed with miRNA chip. Results: (1)In Boyden chamber invasion assay, the cell invasion rate of CD133(+)CD44(+) laryngeal cancer stem cells was obviously higher (80.2%±2.3% vs. 63.9%±3.2%, t=5.011, P=0.027); (2)CD133(+)CD44(+) laryngeal cancer stem cells also had higher mobility in cell migration assay (82.9%±1.1% vs. 70.9%±0.6%, t=4.514, P=0.031); (3)In tumor formation assay, the tumor formation rate of CD133(+)CD44(+) laryngeal cancer stem cells was also higher (80% vs. 50%). What's more, we identified 15 miRNAs that were significantly upregulated in CD133(+)CD44(+) laryngeal cancer stem cells and 3 miRNAs that were significantly downregulated in CD133(+)CD44(+) laryngeal cancer stem cells, compared with normal laryngeal cancer stem cells. Conclusions: CD133(+)CD44(+) laryngeal cancer stem cells have stronger invasion, migration and tumorigenic abilities compared with normal laryngeal cancer stem cells, and the difference of miRNAs' expression is one of the possible causes.

[Diagnostic value of HBP, PCT combined with APACHE â ¡ score respectively in ventilator-associated pneumonia].

Objective: To evaluate the diagnostic value of the heparin-binding protein (HBP), procalcitonin (PCT) and acute physiology and chronic health evaluation Ⅱ (APACHE Ⅱ) score in ventilator-associated pneµmonia (VAP). Methods: A total of 160 patients who required tracheotomy or intubation and assisted breathing with invasive mechanical ventilator from the First Affiliated Hospital of Zhengzhou University from January 2015 to January 2017 was included in this prospective study,and divided into VAP group and no-VAP group based on if VAP happened or not; the VAP group was further divided into deterioration group and improvement group based on the curative effect after anti-infective treatment for 1 week. A total of 40 community acquired pneumonia (CAP) patients and 30 healthy volunteers were also included as control groups. The levels of HBP and PCT in blood of the subjects were tested with enzyme-linked immuno sorbent assay (ELISA) and chemiluminescence immunoassay (ECLIA) respectively, APACHE Ⅱ score was utilized to assess the severity of illness. The difference of HBP, PCT levels and APACHE Ⅱ score among the groups were analyzed. Receiver operating characteristic(ROC) curve was utilized to analyze the diagnostic value of HBP, PCT, APACHE Ⅱ score in VAP. Results: A total of 230 subjects participated in this study, including 68 VAP patients, 92 non-VAP patients, 40 CAP patients and 30 healthy volunteers. Before administration of mechanical ventilation, there were no statistically significant differences in HBP, PCT and APACHE Ⅱ score between VAP group and non-VAP group (all P>0.05). The levels of HBP,PCT and APACHE Ⅱ score were (41.4±21.3) µg/L,(0.355±0.254) µg/L,(13.4±2.5) respectively when the VAP was diagnosed,which were higher than those within the first 12 h of mechanical ventilation (7.3±2.7) µg/L, (0.080±0.038) µg/L, (8.4±2.0), all P<0.001). The HBP, PCT and APACHE Ⅱ score had no significant difference between within the first 12 h of mechanical ventilation and after mechanical ventilation in non-VAP group (all P>0.05). The levels of HBP was positively correlated with PCT and APACHE Ⅱ score (r=0.82, 0.68, all P<0.001). In deterioration group,the HBP,PCT and APACHE Ⅱ score after 1 week of anti-infective treatment were higher than those when the VAP was diagnosed (all P<0.001). No matter it is when the VAP was diagnosed or after anti-infective treatment for 1 week,the levels of HBP, PCT and APACHE Ⅱ score in deterioration group were higher than those in the improvement group (all P<0.001). The area under curve (AUC) of HBP+APACHE Ⅱ score, PCT+APACHE Ⅱ score for VAP diagnosis was 0.98, 0.95 respectively. The sensitivity of HBP+APACHE Ⅱ score in the diagnosis of VAP was lower than PCT+APACHE Ⅱ score (94.1% vs 95.6%),and the specificity was higher (92.4% vs 82.6%). Conclusion: The diagnostic value of HBP+APACHE Ⅱ score for early VAP is superior to PCT+APACHE Ⅱ score.

Gut microbiota and obesity-associated osteoarthritis.

Obesity is a well-known primary risk factor for osteoarthritis (OA). In recent decades, the biomechanics-based theoretical paradigm for the pathogenesis of obesity-associated OA has been gradually but fundamentally modified. This modification is a result of accumulating evidence that biological factors also contribute to the etiology of the disease. The gut microbiota is a complicated ecosystem that profoundly influences the health of the host and can be modulated by the combined effects of environmental stimuli and genetic factors. Recently, enteric dysbacteriosis has been identified as a causal factor in the initiation and propagation of obesity-associated OA in animal models. Gut microbes and their components, microbe-associated lipid metabolites, and OA interact at both systemic and local levels through mechanisms that involve interplay with the innate immune system. However, the demonstration of causality in humans will require further studies. Nonetheless, probiotics, prebiotics, dietary habits and exercise, which aid the restoration of a healthy microbial community, are potential therapeutic approaches in the treatment of obesity-associated OA.

[Predictive value of Wells Score, Revised Geneva Score combined with D-dimer for Pulmonary Embolism in patients with acute exacerbation of chronic obstructive pulmonary disease].

Objective: To evaluate the predictive value of Wells score, revised Geneva score combined with D-dimer for the risk of pulmonary embolism in patients with acute exacerbation of chronic obstructive pulmonary disease (AECOPD). Methods: In this study, 234 AECOPD patients underwent CT pulmonary angiography from March 1, 2013 to December 31, 2015 in the First Affiliated Hospital of Zhengzhou University. The basic data of the patients were collected and the patients were classified into AECOPD combined with pulmonary embolism group(pulmonary embolism group) and AECOPD group according to CT pulmonary angiography results. All patients were scored by Wells score and revised Geneva score. The receiver operating characteristic (ROC) curves were generated and the Z test was applied to evaluate the predictive value by comparing the area under the ROC curves (AUC). Results: Totally 32(13.7%) patients had pulmonary embolism out of the 234 AECOPD patients. The AUC by Wells score, revised Geneva score, D-dimer, Wells score + D-dimer, revised Geneva score + D-dimer were 0.869 (95% CI: 0.789-0.949), 0.710 (95% CI: 0.588-0.832), 0.866 (95% CI: 0.790-0.941), 0.926 (95% CI: 0.874-0.977), 0.855 (95% CI: 0.751-0.959). The AUC of Wells score and D-dimer were significantly greater than that of revised Geneva score (Z=2.14, 2.12, both P<0.05); the AUC of Wells score + D-dimer was significantly greater than revised Geneva score + D-dimer (Z=2.73, P<0.05). Conclusion: The predictive value of Wells score + D-dimer for pulmonary embolism in AECOPD patients is higher than revised Geneva score + D-dimer.

[The levels of neuropeptide S in the brain of asthmatic mice with anxiety and the relationship with the inflammatory mediators].

Objective: To investigate the levels of neuropeptide S in the brain of asthmatic mice with anxiety and the effects of inflammatory mediatores on changes of neuropeptide S in in vitro experiments. Methods: According to the random number table method, 40 BALB/C mice were randomly divided into 4 groups: the control group, the asthma group, the anxiety group and the asthma and anxiety group. The relative expressions of neuropeptide S mRNA in the brain tissue of each group were detected by quantitative real-time polymerase chain reaction(QRT-PCR). Rat cortex neurons obtained by primary culture were divided into 4 groups: the PBS control group, the interleukin-1 beta group, the interleukin-6 group and the tumor necrosis factor-alpha group. After stimulation with inflammatory cytokines the mRNA expressions of neuropeptide S were measured by QRT-PCR and neuropeptide S levels in the cell culture supernatants were measured by emzyme linked immunosorbent assay(ELISA). Results: The relative expressions of neuropeptide S mRNA were decreased in the anxiety group(0.87±0.05) and the asthma and anxiety group(0.79±0.03)compared with the control group(1.00±0.05)and the asthma group(0.96±0.06), most notably in the asthma and anxiety group (all P<0.05). Compared to the PBS control group[(1.00±0.06), (50.6±1. 8)ng/L] and the interleukin-1 beta group[(0.94±0.08), (49.5±1.0)ng/L], the levels of neuropeptide S mRNA and neuropeptide S were decreased in the interleukin-6 group[(0.88±0.07), (45.4±1.2)ng/L] and the tumor necrosis factor-alpha group[(0.86±0.07), (46.0±1.0)ng/L](all P<0.05). There were no significant differences between the interleukin-1 beta group and the PBS control group(all P>0.05). Conclusions: Up-regulated interleukin-6 and tumor necrosis factor-alpha in asthma can inhibit the secretion of neuropeptide S in neuronal cells. The decline of brain neuropeptide S, which has anti-anxiety effect, may lead to the occurrence of anxiety, which may be a potential mechanism of comorbidity of asthma and anxiety.

[The immunological effects of phthalanilic acid on mice].

OBJECTIVE: To explore the effects of phthalanilic acid on immune system in mice from the respects of blood, tissues, cell and cytokines. And to find sensitive index of immunological effects and offer experimental data for toxicological safety evaluation. METHODS: 60 balb/c mice were randomly divided into 4 groups. The mice in control group were given soybean oil. The mice in group 2 to 4 were given phthalanilic acid at dose 30 mg/kg, 100 mg/kg and 300 mg/kg by gavage respectively for 28 days. After 24 hours of the last contamination, the histopathology of spleen and thymus, immunologic factors and cell multiplication of lymphocyte were analysed. The data were analysed by SPSS. RESULTS: After contamination for 28 days, 300 mg/kg phthalanilic acid could cause that the cell multiplication of lymphocyte were inhibited. Spleens were damaged at the dose of 100 mg/kg. The concentration of IFN-γ and IL-4[ (843.31±14.81) pg/ml and (1174.44±7.32) pg/ml] in thymus were increased significantly (P<0.05) at the dose of 30 mg/kg. CONCLUSION: Different doses of phthalanilic acid may damnify the immune system of mice at different degrees for 28 days continuous contamination. Phthalanilic acid might have immunotoxicity.

Correlation between polymorphisms in the glucocorticoid receptor gene NR3C1 and susceptibility to asthma in a Chinese population from the Henan Province.

The aim of this study was to investigate the association between four single nucleotide polymorphisms in NR3C1 (Tth111I, BclI, ER22/23EK, and N363S), which encode the glucocorticoid receptor, and asthma susceptibility in patients from the Henan Province of China. Three hundred and twenty-eight patients with asthma and 60 healthy volunteers were recruited to this study. The target SNPs were genotyped by polymerase chain reaction (PCR)-high resolution melting and PCR-restriction fragment length polymorphism. The frequencies of the AA (8.84%) and GG (30.79%) genotypes of Tth111I were higher, and that of the AG genotype was lower (60.37%), in the asthma patients compared to that seen in healthy controls (5.00, 26.67, and 68.33%, respectively). On the other hand, asthma patients showed higher frequencies of the AA genotype (78.05%) of N363S, and lower frequencies of the AG and GG genotypes (15.55 and 6.40%), compared to healthy volunteers (71.67, 18.33, and 10.00%, respectively). Neither of these differences were found to be statistically significant. Moreover, we observed no significant differences in the genotype or allele frequencies of the BclI and ER22/23EK SNPs between the patient and control groups. In conclusion, SNPs in NR3C1 were not significantly associated with asthma in patients from the Henan Province. Patients showed higher frequencies of the AA and GG genotypes of Tth111I and the AA genotype of the N363S SNP compared to healthy volunteers, although these differences were not significant.

Regulatory effect of iron regulatory protein-2 on iron metabolism in lung cancer.

Iron metabolism plays an important role in the pathogenesis of lung cancer. This study aimed to investigate the effect of gene silencing of iron regulatory protein-2 (IRP2) on mRNA and protein expression of transferrin (Tf), transferrin receptor (TfR), and ferritin (Fn) in A549 lung cancer cells. A549 cells were cultured and divided into a liposome control group, a liposome + oligonucleotide (SCODN) control group, and a Lipofectamine + antisense oligonucleotide (ASODN) group. RT-PCR and Western blotting were used to detect mRNA and protein expression of Tf, TfR, and Fn. We found no significant change in Tf mRNA expression among the 3 groups (P = 0.078). TfR and Fn mRNA expressions in the ASODN group notably decreased compared to the liposome and SCODN groups (P < 0.01). IRP2 and TfR protein expressions in the ASODN group were significantly lower than in the liposome or SCODN groups (P < 0.05), whereas no significant change in Tf protein expression was observed between the 3 groups (P = 0.088). Fn protein expression in the ASODN group was significantly higher than in the liposome or SCODN group (P < 0.05). IRP2 can regulate the expression of TfR and Fn by changing its own protein expression and thereby regulate iron metabolism.

Recurrent splice-site mutation in MBTPS2 underlying IFAP syndrome with Olmsted syndrome-like features in a Chinese patient.

Mutations in MBTPS2 have been reported to cause a broad phenotypic spectrum of X-linked genodermatoses, including IFAP (ichthyosis follicularis; atrichia and photophobia) syndrome (OMIM 308205) with or without BRESHECK (brain anomalies, retardation of mentality and growth, ectodermal dysplasia, skeletal malformations, Hirschsprung disease, ear deformity and deafness, eye hypoplasia, cleft palate, cryptorchidism, and kidney dysplasia/hypoplasia) syndrome, keratosis follicularis spinulosa decalvans (KFSD; OMIM 308800) and an X-linked form of Olmsted syndrome. We report a recurrent intronic mutation in MBTPS2 (c.671-9T>G) in a Chinese patient with the typical triad of IFAP syndrome (i.e. ichthyosis, atrichia and photophobia), along with pachyonychia, palmoplantar and periorificial keratoderma, which were reminiscent of Olmsted syndrome. Interestingly, this mutation was previously reported in two cases of IFAP without keratoderma, which suggests clinical heterogeneicity of the same mutation in MBTPS2. The concomitance of Olmsted syndrome-like features in this patient with IFAP may challenge the existence of the X-linked form of Olmsted syndrome as an independent condition.

Effect of glycyrrhizin on CYP2C19 and CYP3A4 activity in healthy volunteers with different CYP2C19 genotypes.

The objective of this study was to investigate the interaction between glycyrrhizin and omeprazole and observe the effects of glycyrrhizin on CYP2C19 and CYP3A4 activities in healthy Chinese male volunteers with different CYP2C19 genotypes. Eighteen healthy subjects (six CYP2C19*1/*1, five CYP2C19*1/*2, one CYP2C19*1/*3, five CYP2C19*2/*2 and one CYP2C19*2/*3) were enrolled in a two-phase randomized crossover trial. In each phase, all subjects received placebo or glycyrrhizin salt tablet 150 mg twice daily for 14 consecutive days. The pharmacokinetics of omeprazole (20 mg orally on day 15) was determined for up to 12 h following administration by high-performance liquid chromatography. After 14-day treatment of glycyrrhizin, plasma omeprazole significantly decreased, and those of omeprazole sulfone significantly increased. However, plasma concenetrations of 5-hydroxyomeprazole did not significantly change. The ratio of AUC(0-infinity) of omeprazole to omeprazole sulfone decreased by 43.93% + or - 13.56% (p = 0.009) in CYP2C19*1/*1, 44.85% + or - 14.84% (p = 0.002) in CYP2C19*1/*2 or *3 and 36.16% + or - 7.52% (p < 0.001) in CYP2C19*2/*2 or *3 while those of omeprazole to 5-hydroxyomeprazole did not change significantly in all three genotypes. No significant differences in glycyrrhizin response were found among CYP2C19 genotypes. Glycyrrhizin induces CYP3A4-catalyzed sulfoxidation of omeprazole and leads to decreased omeprazole plasma concentrations, but has no significant impact on CYP2C19-dependent hydroxylation of omeprazole.

Effect of St. John's wort supplementation on the pharmacokinetics of bupropion in healthy male Chinese volunteers.

The objective of this study was to investigate the effects of continuous St. John's wort administration on single-dose pharmacokinetics of bupropion, a substrate of cytochrome P450 (CYP) 2B6, in healthy Chinese volunteers. Eighteen unrelated healthy male subjects participated in this study. The single-dose pharmacokinetics of bupropion and hydroxybupropion were determined before (control) and after a long-term period of St. John's wort intake (325 mg, three times a day for 14 days). Plasma concentrations of bupropion and hydroxybupropion were determined before and at 0.5, 1, 2, 3, 4, 5, 6, 8, 10, 12, 24, 36, 48, 60 and 72 h after dosing. St. John's wort treatment decreased the area under the concentration versus time curve extrapolated to infinity of bupropion in healthy volunteers from 1.4 microg.h ml(-1) (95% confidence interval [CI] = 1.2-1.6 microg.h ml(-1)) after bupropion alone to 1.2 microg.h ml(-1) (95% CI = 1.1-1.3 microg.h ml(-1)) during St. John's wort treatment. St. John's wort treatment increased the oral clearance of bupropion from 108.3 l h(-1) (95% CI = 95.4-123.0 l h(-1)) to 130.0 l h(-1) (95% CI = 118.4-142.7 l h(-1)). No change in the time to peak concentration (t(max)) and the blood elimination half-life (t(1/2)) of bupropion was observed between the control and St. John's wort-treated phases. However, the half-life of hydroxybupropion between two phases had a significant difference by a Student's t test after logarithmic transformation. St. John's wort treatment decreased the half-life of hydroxybupropion from 26.7 h (95% CI = 23.8-29.9 h) to 24.4 h (95% CI = 21.9-27.3 h). St. John's wort decreased, to a statistically significant extent, the plasma concentrations of bupropion, probably mainly by increasing the clearance of bupropion.

Effect of bifendate on the pharmacokinetics of talinolol in healthy subjects.

To evaluate the effect of bifendate on the pharmacokinetics of talinolol, 16 unrelated male healthy subjects were selected for this study. After repeated oral administration of placebo or bifendate (three times daily for 14 days), the plasma concentration of talinolol was measured by high-performance liquid chromatography-electrospray mass spectrometry. This study was carried out in a randomized, single-blinded, placebo-controlled, crossover manner. After the treatment of bifendate, the area under the curve (AUC(0-infinity)) was decreased significantly by 11.2% (90% confidence interval (CI), 7.3-12.4%; p = 0.001), and the Cmax value of talinolol was decreased by approximately 9.7% (90% CI, 5.5-11.4%; p = 0.001). The oral clearance of talinolol was increased significantly by 13.1% (90% CI, 8.0-14.4%; p = 0.001). The results suggest that the treatment of bifendate can decrease the plasma concentration of talinolol in healthy subjects.