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Pharmacokinetics and Bioequivalence of Clopidogrel Hydrogen Sulfate Tablets in Fed and Fasted Conditions: An Open-Label, Randomized, Semireplicated Crossover Study in Healthy Chinese Volunteers.
Pei, T, Yang, J, Hu, C, Chen, X, Gong, S, Hu, X, Li, L, Zhang, L
Clinical pharmacology in drug development. 2020;(7):813-820
Abstract
Clopidogrel is an antiplatelet drug with high intraindividual variability in systemic exposure and efficacy. It has been used for treating atherosclerosis and acute coronary syndrome and in preventing stent restenosis and thrombotic complications after stent implantation in clinical practice for nearly 20 years. In this study we aimed to evaluate the bioequivalence of 2 clopidogrel hydrogen sulfate formulations (75-mg tablets) under fed (n = 66) and fasted (n = 66) conditions by using the reference-scaled average bioequivalence method. An open-label, randomized, 3-sequence and 3-period crossover (3×3), semireplicated study was designed and conducted. Clopidogrel concentration of plasma samples was measured by high-precision liquid chromatography and tandem mass spectrometry. The pharmacokinetic parameters were derived by a noncompartmental model. In the fed condition the geometric least-squares mean ratios of peak concentration (Cmax ) and area under the concentration-time curve (AUC0-t ) were, respectively, 103.38% and 98.97%, and the corresponding 90%CIs were 95.68% to 111.70% and 94.67% to 103.47%. In the fasted condition the geometric least squares mean ratios of Cmax and AUC0-t were, respectively, 106.53% and 105.77%, and the corresponding 90%CIs were 97.62% to 116.25% and 96.96% to 115.38%. According to the criteria for bioequivalence (80.00% to 125.00%), the test formulations of clopidogrel and Plavix were determined to be bioequivalent.
2.
Determining the optimal fasting glucose target for patients with type 2 diabetes: Results of the multicentre, open-label, randomized-controlled FPG GOAL trial.
Yang, W, Ma, J, Yuan, G, Li, L, Zhang, M, Lu, Y, Ye, X, Song, W, Liu, M, Wu, J, et al
Diabetes, obesity & metabolism. 2019;(8):1973-1977
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Abstract
The optimal fasting blood glucose (FBG) target of achieving HbA1c less than 7.0% in type 2 diabetes (T2D) patients remains controversial. This open-label trial randomized (1:3:3) 947 adults with uncontrolled T2D (HbA1c >7% to ≤10.5%) who were using one to three oral antidiabetic drugs to achieve an FBG target of 3.9 < FBG ≤5.6 mmol/L (Group 1), 3.9 < FBG ≤6.1 mmol/L (Group 2) or of 3.9 < FBG ≤7.0 mmol/L (Group 3). Targets were achieved using a pre-defined insulin glargine 100 U/mL titration scheme. The primary endpoint was proportion of patients achieving HbA1c <7.0% at 24 weeks. At 24 weeks, 44.4%, 46.1% and 37.7% of patients achieved HbA1c <7.0% in Groups 1, 2 and 3, respectively (P = 0.017; Group 2 vs Group 3). Alert hypoglycaemia (glucose ≤3.9 mmol/L) was significantly more frequent in Group 1 than in Group 3 (38.9 vs 23.3%; P < 0.001) but was not in Group 2 vs Group 3 (27.5% vs 23.3%; P = 0.177). Clinically important hypoglycaemia (glucose ≤3.0 mmol/L) was reported in 4.8%, 2.0% and 3.8% of patients in Groups 1, 2 and 3, respectively. In conclusion, the optimal FBG target for most Chinese patients with T2D appears to be 3.9-6.1 mmol/L.