Prediction of Fluoroquinolone-Induced Elevation in Serum Creatinine Levels: A Case of Drug–Endogenous Substance Interaction Involving the Inhibition of Renal Secretion
| العنوان: | Prediction of Fluoroquinolone-Induced Elevation in Serum Creatinine Levels: A Case of Drug–Endogenous Substance Interaction Involving the Inhibition of Renal Secretion |
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| المؤلفون: | Takashi Izumi, Nobuyuki Murayama, Katsuhisa Inoue, Yuichiro Imamura, Hiroyuki Kusuhara, Yuichi Sugiyama, Hiroaki Yuasa, Atsushi Kurihara, Noriko Okudaira, Osamu Okazaki |
| المصدر: | Clinical Pharmacology & Therapeutics. 89:81-88 |
| بيانات النشر: | Springer Science and Business Media LLC, 2010. |
| سنة النشر: | 2010 |
| مصطلحات موضوعية: | Adult, Male, medicine.medical_specialty, Pyrrolidines, Organic Cation Transport Proteins, Organic anion transporter 1, Renal function, Organic Anion Transporters, Sodium-Independent, Quinolones, Models, Biological, Cell Line, Kidney Tubules, Proximal, Young Adult, chemistry.chemical_compound, Double-Blind Method, Pharmacokinetics, Membrane Transport Modulators, Internal medicine, medicine, Humans, Pharmacology (medical), Antibacterial agent, Pharmacology, Kidney, Creatinine, biology, Reabsorption, Organic Cation Transporter 2, Middle Aged, Anti-Bacterial Agents, Kinetics, HEK293 Cells, Endocrinology, medicine.anatomical_structure, chemistry, Renal physiology, biology.protein, Female, Fluoroquinolones |
| الوصف: | The aim of this study was to examine the mechanism underlying the elevation in serum creatinine levels caused by a novel des-fluoro(6)-quinolone antibacterial agent, DX-619, in healthy subjects. hOCT2 showed a prominent uptake of creatinine (K(m) = 56.4 mmol/l) among renal organic ion transporters. DX-619 is a potent inhibitor of hOCT2 (K(i) = 0.94 micromol/l), hMATE1 (0.82 µmol/l), and hMATE2-K (0.10 micromol/l). The pharmacokinetic model involving the inhibition of hOCT2 (model 1), hOCT2, and MATE1 or MATE2-K (model 2) could predict the elevation in serum creatinine levels in individual subjects receiving DX-619. This assumes that a significant contribution of tubular secretion (59, 38, and 31%) and reabsorption ranged from 3-50, 4-30, and 5-21% in model 1, -2a (hOCT2/hMATE1), and -2b (hOCT2/hMATE2-K), respectively, for creatinine. In conclusion, DX-619, at its therapeutic dose, is able to inhibit hOCT2, hMATE1, and hMATE2-K, leading to a significant inhibition of tubular secretion of creatinine and consequently to elevation of serum creatinine levels. |
| تدمد: | 1532-6535 0009-9236 |
| الوصول الحر: | https://explore.openaire.eu/search/publication?articleId=doi_dedup___::dcfaad7adf274dd11099a4e3d48e1f85Test https://doi.org/10.1038/clpt.2010.232Test |
| رقم الانضمام: | edsair.doi.dedup.....dcfaad7adf274dd11099a4e3d48e1f85 |
| قاعدة البيانات: | OpenAIRE |
| تدمد: | 15326535 00099236 |
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