کد مقاله | کد نشریه | سال انتشار | مقاله انگلیسی | نسخه تمام متن |
---|---|---|---|---|
2562803 | 1127289 | 2010 | 7 صفحه PDF | دانلود رایگان |
عنوان انگلیسی مقاله ISI
Up-regulation of renal Mdr1 and Mrp2 transporters during amiodarone pretreatment in rats
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موضوعات مرتبط
علوم پزشکی و سلامت
داروسازی، سم شناسی و علوم دارویی
داروشناسی
پیش نمایش صفحه اول مقاله
![عکس صفحه اول مقاله: Up-regulation of renal Mdr1 and Mrp2 transporters during amiodarone pretreatment in rats Up-regulation of renal Mdr1 and Mrp2 transporters during amiodarone pretreatment in rats](/preview/png/2562803.png)
چکیده انگلیسی
Although amiodarone (AMD) is known to produce drug-drug interactions through inhibition of transporter-mediated excretion of drugs, its impact on these mechanisms during chronic treatment has not been described yet. Therefore, the aim of this study was to investigate the influence of AMD pretreatment on the main multidrug transporting proteins, Mdr1 and Mrp2, in the liver and kidney. The expression of the transporters and pharmacokinetics of their substrates, rhodamine-123 (Rho123) and endogenous conjugated bilirubin (CB), were evaluated in rats after either AMD oral pretreatments (4-14 days) or single intravenous bolus. AMD pretreatment of all durations up-regulated renal Mdr1 and Mrp2 protein expression to 155-190% and 152-223% of the control values, respectively. In agreement, we observed a corresponding increase in renal clearance of both substrates. Hepatic expression was increased only for Mdr1 to 234-270% of controls, which was associated with increased biliary elimination of amiodarone without change in Rho123 biliary clearance. Interestingly, hepatic expression of another Mdr transporter, Mdr2, was progressively decreased by amiodarone administration. Acute administration of AMD reduced Rho123 biliary clearance by 64%. Our results indicate that repeated administration of AMD to rats is associated with significant increase in hepatic and renal expression of Mdr1 and Mrp2 transporters, which may contribute to variability in pharmacokinetics of AMD and simultaneously applied drugs.
ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: Pharmacological Research - Volume 61, Issue 2, February 2010, Pages 129-135
Journal: Pharmacological Research - Volume 61, Issue 2, February 2010, Pages 129-135
نویسندگان
Jolana Cermanova, Leos Fuksa, Eva Brcakova, Milos Hroch, Otto Kucera, Gabriela Kolouchova, Petra Hirsova, Jana Malakova, Frantisek Staud, Jirina Martinkova, Zuzana Cervinkova, Stanislav Micuda,