The Impact of Inflammation on the In Vivo Activity of the Renal Transporters OAT1/3 in Pregnant Women Diagnosed with Acute Pyelonephritis.
The Impact of Inflammation on the In Vivo Activity of the Renal Transporters OAT1/3 in Pregnant Women Diagnosed with Acute Pyelonephritis.
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炎症对被诊断患有急性肾盂肾炎的孕妇OAT1/3体内活性的影响。
DOI：
10.3390/pharmaceutics15102427
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发表时间：
2023-10-05
期刊：
影响因子：
5.4
通讯作者：
Lanchote VL
中科院分区：
文献类型：
--
作者：
Benzi JRL;Melli PPDS;Duarte G;Unadkat JD;Lanchote VL
炎症可以调节肝脏药物代谢酶和转运蛋白。炎症对肾脏药物转运蛋白的影响仍有待阐明。我们的目的是量化炎症（由急性肾盂肾炎引起）对体内肾OAT 1/3活性的影响，使用探针药物呋塞米。孕妇（妊娠中期或晚期）在急性肾盂肾炎期间（1期; n = 7）和缓解后（2期; n = 7;通过静脉注射头孢呋辛750 mg TID治疗3-7天）接受单次口服呋塞米40 mg，间隔10 - 14天。与II期相比，I期的IL-6、IFN-γ、TNF-α、MCP-1和C反应蛋白血浆浓度更高。与II期相比，I期妊娠女性的呋塞米CL分泌（3.9 [43.4] vs. 6.7 [43.8] L/h）和葡萄糖醛酸苷形成清除率（1.1 [85.9] vs. 2.3 [64.1] L/h）的几何平均值[CV%]较低。炎症使肾OAT 1/3（介导呋塞米CL分泌）和UGT 1A 9/1A 1（介导呋塞米葡糖苷酸形成）的体内活性分别降低约40%和54%，推测是通过升高血浆细胞因子浓度实现的。窄治疗窗OAT药物底物的给药方案可能需要在炎性疾病期间进行调整。
Inflammation can regulate hepatic drug metabolism enzymes and transporters. The impact of inflammation on renal drug transporters remains to be elucidated. We aimed to quantify the effect of inflammation (caused by acute pyelonephritis) on the in vivo activity of renal OAT1/3, using the probe drug furosemide. Pregnant women (second or third trimester) received a single oral dose of furosemide 40 mg during acute pyelonephritis (Phase 1; n = 7) and after its resolution (Phase 2; n = 7; by treatment with intravenous cefuroxime 750 mg TID for 3–7 days), separated by 10 to 14 days. The IL-6, IFN-γ, TNF-α, MCP-1, and C-reactive protein plasma concentrations were higher in Phase I vs. Phase II. The pregnant women had a lower geometric mean [CV%] furosemide CLsecretion (3.9 [43.4] vs. 6.7 [43.8] L/h) and formation clearance to the glucuronide (1.1 [85.9] vs. 2.3 [64.1] L/h) in Phase 1 vs. Phase 2. Inflammation reduced the in vivo activity of renal OAT1/3 (mediating furosemide CLsecretion) and UGT1A9/1A1 (mediating the formation of furosemide glucuronide) by approximately 40% and 54%, respectively, presumably by elevating the plasma cytokine concentrations. The dosing regimens of narrow therapeutic window OAT drug substrates may need to be adjusted during inflammatory conditions.
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影响因子：
7.3
作者：
García-Torre A;Bueno-García E;López-Martínez R;Rioseras B;Díaz-Molina B;Lambert JL;Quirós C;Alonso-Álvarez S;Alonso-Arias R;Moro-García MA
通讯作者：
Moro-García MA
影响因子：
5.8
作者：
Kerdpin, Oranun;Knights, Kathleen M.;Miners, John O.
通讯作者：
Miners, John O.
影响因子：
3.3
作者：
Jim B;Garovic VD
通讯作者：
Garovic VD
DOI：
10.1111/cts.12808
发表时间：
2020-11
期刊：
Clinical and translational science
影响因子：
--
作者：
Cestari RN;de Oliveira RDR;de Souza FFL;Pippa LF;Nardotto GHB;Rocha A;Donadi EA;Lanchote VL
通讯作者：
Lanchote VL
DOI：
10.3390/medicina58121780
发表时间：
2022-12-02
期刊：
Medicina (Kaunas, Lithuania)
影响因子：
--
作者：
Klinkmann G;Klammt S;Jäschke M;Henschel J;Gloger M;Reuter DA;Mitzner S
通讯作者：
Mitzner S