A specific ultra-high-performance liquid chromatography/quadrupole time-of-flight mass spectrometry (UHPLC-Q-TOF-MS/MS) method has been described for the simultaneous determination of the metabolites of tacrine, bupropion, diclofenac, dextromethorphan and midazolam, which are the five probe drugs of the five cytochrome P450 (CYP450) isoforms CYP1A2, CYP2B, CYP2C11, CYP2D1 and CYP3A4.The inhibition degree was determined by calculating the IC 50 . The chromatographic separation was performed on a C 18 column with a mobile phase consisting of 0.1% formic acid and acetonitrile. The mass spectrometric analysis was conducted in positive electrospray ionization mode. The IC 50 values of CYP1A2, CYP2B, CYP2C11, CYP2D1 and CYP3A were 113.4, 83.78, 22.50, 9.081 and 52.76 μmol L À1 , respectively. The in vitro results demonstrated that vindoline could inhibit CYP2D1 activity in rats, and weak inhibitory effect on CYP2C11 and CYP3A, but had no obvious effects on CYP1A2 and CYP2B.
Objectives: The aim of this study was to indirectly compare the efficacy and safety of mirabegron and vibegron in patients with overactive bladder.Methods: A systematic search was performed on Pubmed, Web of Science, Embase, and the Cochrane Central Register of Controlled Trials databases to identify studies from the date of database inception to January 1, 2022. All randomized controlled trials comparing mirabegron or vibegron with tolterodine, imidafenacin, or placebo were eligible. One reviewer extracted data, and a second reviewer checked. Included trials were assessed for similarity, and networks were developed using Stata 16.0 software. Mean differences for continuous variables and odds ratios for dichotomous variables together with their 95% confidence intervals (CIs) were used to rank treatments and compare the differences, respectively.Results: A total of 11 randomized controlled trials and 10 806 patients were included. For each outcome, results for all licensed treatment doses were included.Both vibegron and mirabegron were more efficacious than placebo at reducing the frequency of micturition, incontinence, urgency, urgency incontinence, and nocturia.Vibegron was more efficacious than mirabegron in reducing mean voided volume/ micturition (95% CI [5.15, 14.98]). Safety outcomes for vibegron and mirabegron were similar to those in the placebo group, except for mirabegron, which had a higher risk of nasopharyngitis and cardiovascular adverse events than placebo.Conclusions: Both drugs seem to be comparable and well tolerated, particularly as direct comparisons are not available. However, vibegron may be more effective than mirabegron in reducing mean voided volume.mirabegron, network meta-analysis, overactive bladder, randomized controlled trials, vibegron | INTRODUCTIONOveractive bladder (OAB) is defined as "urgency, with or without urgency incontinence usually accompanied by frequent micturition and nocturia." 1 OAB pathogenesis is diverse, but in most instances, the underlying cause is unclear. OAB is a common health disorder with a worldwide prevalence in adults of 10%-20%, which has gradually increased. 2,3 OAB is a common urological disease, and it seriously affects the quality of life of patients. Current treatments for OAB include behavioral therapy, pharmacological treatment, minimally
The objection of this study was to investigate the effects of vindoline(VDL) on the cytochrome P450 (CYP 450) isoforms (CYP1A2, 2B, 2C11, 2D1 and 3A) in rats. Firstly, the rats were randomly divided into VDL pretreatment group and blank group, each group had six rats. VDL pretreatment group was administrated VDL (20 mg·kg-1) by oral gavage for fifteen days consecutively, and the equivalent CMC-Na solution without VDL was given to the blank group by gavage. Secondly, a cocktail of caffeine, bupropion, diclofenac, dextromethorphan and midazolam was then administered on the sixteenth day. Finally, blood samples were collected at the specified time point, and the plasma concentration of the probe drug was determined by UHPLC-QTOF-MS/MS. The effects of VDL on the activity of these CYP enzymes in rats were evaluated by pharmacokinetic parameters. VDL pretreatment group compared with the blank group, accelerated the metabolism of diclofenac, and weakened the metabolism of caffeine. These results suggested that VDL could induce the activity of CYP2C11, and inhibits the activity of CYP1A2, but had no significant effects on CYP2B, CYP2D1 and CYP3A. The results in this study can provide beneficial information for the later clinical application of VDL.
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