scholarly journals Pharmacokinetic Drug‐Drug Interactions Between Trospium Chloride and Ranitidine Substrates of Organic Cation Transporters in Healthy Human Subjects

2019 ◽  
Vol 60 (3) ◽  
pp. 312-323
Author(s):  
Bayew Tsega Abebe ◽  
Michael Weiss ◽  
Christiane Modess ◽  
Tobias Tadken ◽  
Danilo Wegner ◽  
...  
Author(s):  
Buqing Yi ◽  
Igor Nichiporuk ◽  
Matthias Feuerecker ◽  
Gustav Schelling ◽  
Alexander Chouker

2020 ◽  
Vol 22 (1) ◽  
pp. 22
Author(s):  
Matthias Gorecki ◽  
Simon F. Müller ◽  
Regina Leidolf ◽  
Joachim Geyer

Background: The muscarinic receptor antagonist trospium chloride (TCl) is used for pharmacotherapy of the overactive bladder syndrome. TCl is a hydrophilic positively charged drug. Therefore, it has low permeability through biomembranes and requires drug transporters for distribution and excretion. In humans, the organic cation transporters OCT1 and OCT2 and the multidrug and toxin extrusion MATE1 and MATE2-K carriers showed TCl transport. However, their individual role for distribution and excretion of TCl is unclear. Knockout mouse models lacking mOct1/mOct2 or mMate1 might help to clarify their role for the overall pharmacokinetics of TCl. Method: In preparation of such experiments, TCl transport was analyzed in HEK293 cells stably transfected with the mouse carriers mOct1, mOct2, mMate1, and mMate2, respectively. Results: Mouse mOct1, mOct2, and mMate1 showed significant TCl transport with Km values of 58.7, 78.5, and 29.3 µM, respectively. In contrast, mMate2 did not transport TCl but showed MPP+ transport with Km of 60.0 µM that was inhibited by the drugs topotecan, acyclovir, and levofloxacin. Conclusion: TCl transport behavior as well as expression pattern were quite similar for the mouse carriers mOct1, mOct2, and mMate1 compared to their human counterparts.


Nutrients ◽  
2021 ◽  
Vol 13 (2) ◽  
pp. 618
Author(s):  
Riley Larson ◽  
Courtney Nelson ◽  
Renee Korczak ◽  
Holly Willis ◽  
Jennifer Erickson ◽  
...  

Acacia gum (AG) is a non-viscous soluble fiber that is easily incorporated into beverages and foods. To determine its physiological effects in healthy human subjects, we fed 0, 20, and 40 g of acacia gum in orange juice along with a bagel and cream cheese after a 12 h fast and compared satiety, glycemic response, gastrointestinal tolerance, and food intake among treatments. Subjects (n = 48) reported less hunger and greater fullness at 15 min (p = 0.019 and 0.003, respectively) and 240 min (p = 0.036 and 0.05, respectively) after breakfast with the 40 g fiber treatment. They also reported being more satisfied at 15 min (p = 0.011) and less hungry with the 40 g fiber treatment at 30 min (p = 0.012). Subjects reported more bloating, flatulence, and GI rumbling on the 40 g fiber treatment compared to control, although values for GI tolerance were all low with AG treatment. No significant differences were found in area under the curve (AUC) or change from baseline for blood glucose response, although actual blood glucose with 20 g fiber at 30 min was significantly less than control. Individuals varied greatly in their postprandial glucose response to all treatments. AG improves satiety response and may lower peak glucose response at certain timepoints, and it is well tolerated in healthy human subjects. AG can be added to beverages and foods in doses that can help meet fiber recommendations.


1993 ◽  
Vol 148 (6_pt_1) ◽  
pp. 1571-1575 ◽  
Author(s):  
M. Jeffery Mador ◽  
Ulysses J. Magalang ◽  
Angel Rodis ◽  
Thomas J. Kufel

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