Value of ST-segment change in lead aVR in diagnosing left main disease in Non-ST-elevation acute coronary syndrome-A meta-analysis.

BACKGROUND: Previous researches proved that the ST-segment elevation (STE) in lead aVR had great significance on the prediction of severe left main lesion or serious multivessel lesions. The current research is to summarize the published data and evaluate the overall association of STE in lead aVR and left main coronary artery disease (LMD) in Non-ST-elevation acute coronary syndrome. METHODS: Literature searching was performed in the online database, and a systematic review was conducted based on the searched results. Meaningful STE in lead aVR was summarized and analyzed for odds ratio (OR) and 95% confidence intervals (95% CI). RESULTS: Twenty-seven articles were included for final data analysis. Compared with STE < 0.05, STE ≥ 0.05 mV was associated with a higher incidence rate of LMD (OR = 6.64, 95% CI: 4.80 ~ 9.17), and the degree of STE in lead aVR was significantly associated with LMD. Myocardial infarction was more likely to occur in patients with STE ≥ 0.05 mV than in patients with STE < 0.05 mV (OR = 3.12, 95% CI: 1.73 ~ 5.62). CONCLUSIONS: The STE in lead aVR and the degree of STE are independent predictors in diagnosing LMD or myocardial infarction.

Bioequivalence of two tacrolimus formulations under fasting conditions in healthy male subjects.

BACKGROUND: Tacrolimus is a macrolide immunosuppressant indicated for prophylaxis of transplant rejection. The European regulatory authorities require comparative bioavailability studies with an innovator product to grant marketing authorization of generic products. OBJECTIVE: The purpose of this study was to test the bioequivalence of generic (test) and innovator (reference) tacrolimus capsules. METHODS: Two open-label, 2-period, single-dose, crossover studies compared 0.5 mg and 5 mg capsule test formulations of tacrolimus with reference products in fasting, healthy male volunteers. The 2 study periods were separated by a 20-day (0.5 mg) or 21-day (5 mg) washout period. Blood samples were collected for up to 72 (0.5 mg) or 192 (5 mg) hours post-dose. Tacrolimus concentrations in whole blood were determined using a validated LC-MS/MS method. The primary evaluation criteria were C(max) and AUC(0-72) (0.5 mg) or AUC(0-t) (5 mg). Bioequivalence was assumed if the 90% CIs for the test/reference ratios of log-transformed C(max) and AUC values were within the limits specified by existing European guidelines. Data on safety and patient well-being were collected throughout the study. RESULTS: The 90% CIs for 0.5 mg were 102.99%-120.80% for C(max) and 91.51%-105.92% for AUC(0-72); those for 5 mg were 110.61%-120.96% for C(max) and 96.17%-103.55% for AUC(0-t). These values meet the requirements for assuming bioequivalence as defined in the European Medicines Agency guidelines for narrow therapeutic index drugs (80%-125% for C(max) and 90%-111% for AUC). There were no relevant differences in the safety profiles of the test and reference formulations. CONCLUSIONS: In these comparative bioavailability studies of fasting, healthy male volunteers, the test and reference formulations of tacrolimus 0.5 mg and 5 mg capsules were well tolerated and met the requirements of the European regulatory bioequivalence guidelines. Both studies have been submitted for registration with Clinical Trials Registry-India: CTRI application references REF/2011/05/002346 (0.5 mg) and REF/2011/05/002347 (5 mg).