The effect of dipyridamole on the pharmacokinetics of metformin: a randomized crossover study in healthy volunteers

PURPOSE: Concomitant treatment with the glucose-lowering drug metformin and the platelet aggregation inhibitor dipyridamole often occurs in patients with type 2 diabetes mellitus who have suffered a cerebrovascular event. The gastrointestinal uptake of metformin is mediated by the human equilibrative nucleoside transporter 4 (ENT4), which is inhibited by dipyridamole in preclinical studies. We hypothesized that dipyridamole lowers the plasma exposure to metformin. METHODS: Eighteen healthy volunteers (mean age 23 years; 9 male) were randomized in an open-label crossover study. Subjects were allocated to treatment with metformin 500 mg twice daily in combination with dipyridamole slow-release 200 mg twice daily or to metformin alone for 4 days. After a washout period of 10 days, the volunteers were crossed over to the alternative treatment arm. Blood samples were collected during a 10-h period after intake of the last metformin dose. The primary endpoint was the area under the plasma concentration-time curve (AUC0-12h) and the maximum plasma metformin concentration (C max). RESULTS: In healthy subjects, dipyridamole did not significantly affect Cmax nor AUC0-12h of metformin under steady-state conditions. CONCLUSIONS: Previous in vitro studies report that dipyridamole inhibits the ENT4 transporter that mediates gastrointestinal uptake of metformin. In contrast, co-administration of dipyridamole at therapeutic dosages to healthy volunteers does not have a clinically relevant effect on metformin plasma steady-state exposure. This observation is reassuring for patients who are treated with this combination of drugs

Application of Spectral Remote Sensing for Agronomic Decisions

Remote sensing has provided valuable insights into agronomic management over the past 40 yr. The contributions of individuals to remote sensing methods have lead to understanding of how leaf reflectance and leaf emittance changes in response to leaf thickness, species, canopy shape, leaf age, nutrient status, and water status. Leaf chlorophyll and the preferential absorption at different wavelengths provides the basis for utilizing reflectance with either broad-band radiometers typical of current satellite platforms or hyperspectral sensors that measure reflectance at narrow wavebands. Understanding of leaf reflectance has lead to various vegetative indices for crop canopies to quantify various agronomic parameters, e.g., leaf area, crop cover, biomass, crop type, nutrient status, and yield. Emittance from crop canopies is a measure of leaf temperature and infrared thermometers have fostered crop stress indices currently used to quantify water requirements. These tools are being developed as we learn how to use the information provided in reflectance and emittance measurements with a range of sensors. Remote sensing continues to evolve as a valuable agronomic tool that provides information to scientists, consultants, and producers about the status of their crops. This area is still relatively new compared with other agronomic fields; however, the information content is providing valuable insights into improved management decisions. This article details the current status of our understanding of how reflectance and emittance have been used to quantitatively assess agronomic parameters and some of the challenges facing future generations of scientists seeking to further advance remote sensing for agronomic applications