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Dandan Luo Carolyn L. Westhoff Alison B. Edelman Melissa Natavio Frank Z. Stanczyk William J. Jusko 《Contraception》2019,99(4):256-263
Objective
The objective was to evaluate the pharmacokinetics (PKs) of levonorgestrel (LNG)-containing combined oral contraceptives (COCs) in obese women.Study design
We pooled and reanalyzed data from 89 women with different body mass index (BMI) categories from four clinical studies. The LNG and ethinyl estradiol (EE) PKs were analyzed utilizing a zero-order absorption (K0), two-compartment PK model to evaluate key PK parameters in relation to a range of weights, BMI and body surface area (BSA).Results
Increasing of body habitus metrics is correlated with decreasing Cmax (p<.0001) and AUCτ (p<.05) for both LNG and EE, but no correlation was found for Cmin (p≥.17). Increasing weight and BMI were associated with a modest increase (p≤.056) of clearance (CL) and appreciable increases of central volume (V1, p<.05), distribution clearance (CLd, p≤.001) and peripheral volume (V2, p<.0001) for LNG. For EE, increases in CL (p≤.009) were found with greater weight, BMI and BSA. Values of V1, CLd and V2 also increased (p<.0001) in obese subjects. The half-life and steady-state volume were greater among obese women (p<.0001) for both LNG and EE. LNG and EE PK parameters correlated well (p≤.006 for all), indicating that individual subject physiology affected both drugs similarly.Conclusions
The primary effects of obesity on LNG and EE were a modest increase in CL and a marked increase in distribution parameters. We observed no obesity-related differences in trough LNG and EE concentrations.Implications
This population PK analysis demonstrated reduced systemic exposure to LNG/EE oral contraceptives in obese subjects (Cmax and AUCτ); these particular differences are unlikely to lower contraceptive effectiveness among obese women who are correctly using LNG-containing contraceptives. 相似文献4.
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Martin V. Andersen Cooper Moore Peter Søgaard Daniel Friedman Brett D. Atwater Kristine Arges Melissa LeFevre Johannes J. Struijk Joseph Kisslo Samuel E. Schmidt Olaf T. von Ramm 《Ultrasound in medicine & biology》2019,45(5):1197-1207
Recently, we developed a high-frame-rate echocardiographic imaging system capable of acquiring images at rates up to 2500 per second. High imaging rates were used to quantify longitudinal strain parameters in patients with echocardiographically normal function. These data can serve as a baseline for comparing strain parameters in disease states. The derived timing data also reveal the propagation of mechanical events in the left ventricle throughout the cardiac cycle. High-frame-rate echocardiographic images were acquired from 17 patients in the apical four-chamber view using Duke University's phased array ultrasound system, T5. B-Mode images were acquired at 500–1000 images per second by employing 16:1 or 32:1 parallel processing in receive, a scan depth ≤14 cm and an 80° field of view with a 3.5-MegaHertZ (MHz), 96-element linear array. The images were analyzed using a speckle tracking algorithm tailored for high-frame-rate echocardiographic images developed at Aalborg and Duke University. Four specific mechanical events were defined using strain curves from six regions along the myocardial contour of the left ventricle. The strain curves measure the local deformation events of the myocardium and are independent of the overall cardiac motion. We observed statistically significant differences in the temporal sequence among different myocardial segments for the first mechanical event described, myocardial tissue shortening onset (p < 0.01). We found that the spatial origin of tissue shortening was located near the middle of the interventricular septum in patients with echocardiographically normal function. The quantitative parameters defined here, based on high-speed strain measurements in patients with echocardiographically normal function, can serve as a means of assessing degree of contractile abnormality in the myocardium and enable the identification of contraction propagation. The relative timing pattern among specific events with respect to the Q wave may become an important new metric in assessing cardiac function and may, in turn, improve diagnosis and prognosis. 相似文献
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Hongxu Xian Yuan Liu Alexandra Rundberg Nilsson Raphaella Gatchalian Timothy R. Crother Warren G. Tourtellotte Yi Zhang German R. Aleman-Muench Gavin Lewis Weixuan Chen Sarah Kang Melissa Luevanos Dorit Trudler Stuart A. Lipton Pejman Soroosh John Teijaro Juan Carlos de la Torre Moshe Arditi Elsa Sanchez-Lopez 《Immunity》2021,54(7):1463-1477.e11
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