依托泊甙中2个同分异构体杂质的分离与鉴定

从抗肿瘤药依托泊甙（Ｅｔｏｐｏｓｉｄｅ）的原料药中，用相溶度分析方法，结合柱色谱和薄层色谱分离出２个主要杂质，根据ＵＶ、ＩＲ、比旋度、质谱和核磁共振光谱数据，推断其结构均为依托泊甙的同分异构体，分别命名为４α─表依托泊甙和２β─苦依托泊甙。     

2011年版《英国药典》概览

目的简要介绍《英国药典》2011年版的基本情况、编排结构。方法分析比较了《英国药典》2011年版和2010年版的不同。结果与结论英国药典委员会每年都对《英国药典》进行更新和修订,值得学习和借鉴。     

Meta-Analysis of Short vs. Prolonged Dual Antiplatelet Therapy after Drug-Eluting Stent Implantation and Role of Continuation with either Aspirin or a P2Y12 Inhibitor Thereafter

Aim: The optimal duration of dual antiplatelet therapy (DAPT) after drug-eluting stent (DES) implantation is an ongoing debate and novel data has emerged. The aim of this meta-analysis was to assess outcomes of short vs. control DAPT duration. In addition, the role of single antiplatelet therapy (SAPT) after DAPT with either aspirin or P2Y₁₂ inhibitor monotherapy was analyzed. Methods: The authors searched MEDLINE and Cochrane databases and proceedings of international meetings for randomized controlled trials (RCT) comparing ≤ 3 months with ≥ 6 months DAPT after DES implantation. The primary and co-primary outcomes of interest were definite or probable stent thrombosis (ST) and bleeding. In addition, we performed an analysis on studies who continued with either aspirin or P2Y₁₂ monotherapy after DAPT. Results: 9 RCTs comprising 41,864 patients were included and we analyzed a short DAPT duration of median 1.5 months vs. 12.1 months in the control group. The risk for ST was similar with short vs. control DAPT duration (0.5 vs. 0.5%; hazard ratio 1.17[95% CI 0.89-1.54];p=0.26). Bleeding was significantly reduced with short vs. control DAPT duration (1.9 vs. 3.0%; 0.65[0.54-0.77];p＜0.0001). ST was not different between short vs. control DAPT duration in the analysis of the 4 RCTs who continued with aspirin after DAPT and the 5 P2Y₁₂ RCTs, respectively, and no heterogeneity was detected (p=0.861). Bleeding was also reduced with short vs. control DAPT in both the aspirin (1.2 vs. 1.7%; 0.71[0.51-0.99];p=0.04) and P2Y₁₂ inhibitor studies (2.1 vs. 3.4%; 0.62[0.47-0.80];p=0.0003) and no heterogeneity was detected (p=0.515). Conclusions: Our meta-analysis shows that short DAPT ≤ 3 months followed by SAPT reduces bleeding and is not associated with an increase in ST. The results were consistent within the aspirin and P2Y₁₂ SAPT studies.     

Recent Advances in Visualizing Vulnerable Plaque: Focus on Noninvasive Molecular Imaging

Traditional imaging methods in atherosclerosis have focused primarily on anatomic information. Imaging approaches that visualize molecular targets rather than anatomic structures may emphasize biologic aspects of atherosclerosis. Molecular imaging of atherosclerotic lesions has become a crucial experimental tool and is now emerging in the clinical arena. In this review, we briefly highlight the rationale and fundamental principles of molecular imaging. We then discuss the promising imaging modalities, along with their potential limitations, and the molecular targets being investigated in experimental research. Finally, we summarize the most important clinical studies recently performed in humans.     

Posterior box isolation as an adjunctive ablation strategy with the second-generation cryoballoon for paroxysmal atrial fibrillation: a comparison with standard cryoballoon pulmonary vein isolation

Journal of Interventional Cardiac Electrophysiology - The purpose of the study was to evaluate the impact of left atrial posterior wall isolation (LAPWI) in addition to pulmonary vein isolation...     

Effect of fluvoxamine on the pharmacokinetics of roflumilast and roflumilast N-oxide

OBJECTIVE: To investigate the effects of steady-state dosing of fluvoxamine, an inhibitor of cytochrome P450 (CYP) 1A2 and CYP2C19, on the pharmacokinetics of roflumilast, an oral, once-daily phosphodiesterase 4 (PDE4) inhibitor and its pharmacodynamically active metabolite roflumilast N-oxide. METHODS: In an open-label, non-randomised, one-sequence, two-period, two-treatment crossover study, 14 healthy subjects received a single oral dose of roflumilast 500 microg on study day 1. After a 6-day washout period, repeated doses of fluvoxamine 50 mg once daily were given from days 8 to 21. On day 15, roflumilast 500 microg and fluvoxamine 50 mg were taken concomitantly. Percentage ratios of test/reference (reference: roflumilast alone; test: roflumilast plus steady-state fluvoxamine) of geometric means and their 90% confidence intervals for area under the plasma concentration-time curve, maximum plasma concentration (roflumilast and roflumilast N-oxide) and plasma clearance of roflumilast were calculated. RESULTS: Upon co-administration with steady-state fluvoxamine, the exposure to roflumilast as well as roflumilast N-oxide increased by a factor of 2.6 and 1.5, respectively. Roflumilast plasma clearance decreased by a factor of 2.6, from 9.06 L/h (reference) to 3.53 L/h (test). The combined effect of fluvoxamine co-administration on roflumilast and roflumilast N-oxide exposures resulted in a moderate (i.e. 59%) increase in total PDE4 inhibitory activity. CONCLUSION: Co-administration of roflumilast and fluvoxamine affects the disposition of roflumilast and its active metabolite roflumilast N-oxide most likely via a potent dual pathway inhibition of CYP1A2 and CYP2C19 by fluvoxamine. The exposure increases observed for roflumilast N-oxide are suggested to be attributable to CYP2C19 co-inhibition by fluvoxamine and thus, are not to be expected to occur when roflumilast is co-administered with more selective CYP1A2 inhibitors.