Effect of renal ischaemia/reperfusion‐induced acute kidney injury on pharmacokinetics of midazolam in rats
Effect of renal ischaemia/reperfusion‐induced acute kidney injury on pharmacokinetics of midazolam in rats
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肾缺血/再灌注所致急性肾损伤对咪达唑仑在大鼠体内药代动力学的影响
DOI：
10.1111/jphp.13167
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发表时间：
2019
影响因子：
3.3
通讯作者：
Nishida Koyo
中科院分区：
文献类型：
--
作者：
Tokunaga Ayako;Miyamoto Hirotaka;Fumoto Shintaro;Nishida Koyo
目的探讨肾缺血/再灌注(I/R)诱导的急性肾损伤(AKI)对细胞色素P450 3A(CYP3A)活性探针药物咪达唑仑(MDZ)分布的影响。静脉注射MDZ(静脉注射)。大鼠经颈静脉给药，然后采集血样测定血浆中的MDZ浓度。I/R大鼠给药减少，组织浓度无明显变化。此外，在I/R大鼠，MDZ的组织/血浆(T/P)比值增加。I/R大鼠血浆中MDZ游离分数和吲哚硫酸盐(IS)水平明显升高。结论IS对白蛋白结合型MDZ的置换改变了MDZ的游离分数，提高了MDZ的T/P比值。
ObjectivesThis study aimed to investigate the effects of renal ischaemia/reperfusion (I/R)-induced acute kidney injury (AKI) on the distribution of midazolam (MDZ), a probe drug for cytochrome P450 3A (CYP3A) activity.MethodsWe established an AKI model inducing ischaemia of both renal pedicles for 60 min followed by 24-h reperfusion. MDZ was administered intravenously (i.v.) to the rats via the jugular vein, and then, blood samples were collected to determine the plasma concentration of MDZ.Key findingsWhile the plasma concentration of MDZ after i.v. administration was decreased in the I/R rats, the tissue concentration was not altered. In addition, the tissue-to-plasma (T/P) ratio of MDZ was increased in the I/R rats. The unbound fraction of MDZ and the level of indoxyl sulphate (IS) in plasma were elevated in the I/R rats. Furthermore, the unbound fraction of MDZ was significantly increased by the addition of IS.ConclusionsThese results indicated that the displacement of albumin-bound MDZ by IS changed the unbound fraction of MDZ and elevated the T/P ratio of MDZ in I/R rats.
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氧化应激大鼠体内氟伏沙明的药代动力学和脑分布
影响因子：
3.3
作者：
Shinji Kobuchi;K. Fukushima;Yukako Ito;N. Sugioka;K. Takada
通讯作者：
K. Takada
影响因子：
6.7
作者：
Dowling, TC;Briglia, AE;Henrich, WL
通讯作者：
Henrich, WL
低温对大鼠咪达唑仑体外代谢、结合及体内分布的评价
影响因子：
2.1
作者：
Hirotaka Miyamoto;S. Matsueda;Akihiro Moritsuka;K. Shimokawa;Haruna Hirata;M. Nakashima;H. Sasaki;S. Fumoto;K. Nishida
通讯作者：
K. Nishida
DOI：
10.1186/cc7093
发表时间：
2008
期刊：
Critical care (London, England)
影响因子：
--
作者：
Vilay AM;Churchwell MD;Mueller BA
通讯作者：
Mueller BA
DOI：
10.1002/anie.199216361
发表时间：
1992-12-01
期刊：
ANGEWANDTE CHEMIE-INTERNATIONAL EDITION IN ENGLISH
影响因子：
--
作者：
AYALON, A;RABINOVITZ, M;SCOTT, LT
通讯作者：
SCOTT, LT