Academic Journal
Effects of tetraalkylammonium compounds with different affinities for organic cation transporters on the pharmacokinetics of metformin
| العنوان: | Effects of tetraalkylammonium compounds with different affinities for organic cation transporters on the pharmacokinetics of metformin |
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| المؤلفون: | Choi, Min‐Koo, Jin, Qing‐Ri, Jin, Hyo‐Eon, Shim, Chang‐Koo, Cho, Doo‐Yeoun, Shin, Jae‐Gook, Song, Im‐Sook |
| المصدر: | Biopharmaceutics & Drug Disposition ; volume 28, issue 9, page 501-510 ; ISSN 0142-2782 1099-081X |
| بيانات النشر: | Wiley |
| سنة النشر: | 2007 |
| المجموعة: | Wiley Online Library (Open Access Articles via Crossref) |
| الوصف: | The study sought to investigate the effects of tetraalkylammonium (TAA), inhibitors of the organic cation transporters (OCTs) with different affinities, on the pharmacokinetics of metformin. The inhibitory potentials of TAAs on the uptake of metformin were evaluated by determining IC 50 values in MDCK cells over‐expressing OCTs and, to assess in vivo drug interactions, metformin and TAAs were coadministered to rats. Uptake of metformin was facilitated by over‐expression of hOCT1 and hOCT2 and showed saturable processes, indicating that metformin is a substrate of hOCT1 and hOCT2. The IC 50 values of TAAs for hOCT2 were lower than hOCT1 and decreased with increasing alkyl chain length, indicating that the inhibitory potential of TAAs on metformin uptake was greater in hOCT2 than in hOCT1 and increased with increasing alkyl chain length. The plasma concentration of metformin was elevated by the coadministration of tetrapropylammonium (TPrA) and tetrapentylammonium (TPeA), but not by tetramethylammonium (TMA) or tetraethylammonium (TEA). However, the plasma concentrations of TMA, TEA and TPrA were not changed by the coadministration of metformin. In conclusion, in vivo drug interactions between metformin and TAAs were caused only when metformin was coadministered with TAAs showing higher affinities for OCTs. Copyright © 2007 John Wiley & Sons, Ltd. |
| نوع الوثيقة: | article in journal/newspaper |
| اللغة: | English |
| DOI: | 10.1002/bdd.576 |
| الاتاحة: | https://doi.org/10.1002/bdd.576 https://api.wiley.com/onlinelibrary/tdm/v1/articles/10.1002%2Fbdd.576 https://onlinelibrary.wiley.com/doi/pdf/10.1002/bdd.576 |
| Rights: | http://onlinelibrary.wiley.com/termsAndConditions#vor |
| رقم الانضمام: | edsbas.7ECB1412 |
| قاعدة البيانات: | BASE |
| DOI: | 10.1002/bdd.576 |
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