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1.
《Drug metabolism and pharmacokinetics》2020,35(1):56-70
Hepatic uptake mediated by organic anion transporting polypeptide (OATP) 1B1 and 1B3 can serve as a major elimination pathway for various anionic drugs and as a site of drug-drug interactions (DDIs). This article provides an overview of the in vitro approaches used to predict human hepatic clearance (CLh) and the risk of DDIs involving OATP1Bs. On the basis of the so-called extended clearance concept, in vitro–in vivo extrapolation methods using human hepatocytes as in vitro systems have been used to predict the CLh involving OATP1B-mediated hepatic uptake. CLh can be quantitatively predicted using human donor lots possessing adequate OATP1B activities. The contribution of OATP1Bs to hepatic uptake can be estimated by the relative activity factor, the relative expression factor, or selective inhibitor approaches, which offer generally consistent outcomes. In OATP1B1 inhibition assays, substantial substrate dependency was observed. The time-dependent inhibition of OATP1B1 was also noted and may be a mechanism underlying the in vitro–in vivo differences in the inhibition constant of cyclosporine A. Although it is still challenging to quantitatively predict CLh and DDIs involving OATP1Bs from only preclinical data, understanding the utility and limitation of the current in vitro methods will pave the way for better prediction. 相似文献
2.
《Drug metabolism and pharmacokinetics》2019,34(1):87-94
The purpose of this study was to elucidate the involvement of Mate1 in the tubular secretion of trimethoprim and saturation of Mate1-mediated efflux to address the mechanisms underlying the pharmacokinetic drug interactions with trimethoprim. Trimethoprim is a more potent inhibitor of MATE2-K than MATE1 with Ki values (μM) of 0.030–0.28 and 2.4–5.9, respectively. Trimethoprim is a substrate of human MATE1 and MATE2-K with Km values of 2.3 ± 0.9 and 0.018 ± 0.004 μM, and mouse Mate1, but not human OCT2, mouse Oct1 and Oct2. Pyrimethamine significantly reduced the renal clearance (CLR) of trimethoprim (mL/min/kg) from 40.0 ± 5.1 to 20.1 ± 3.7 (p < 0.05). Trimethoprim was given to mice at three infusion rates (150, 500, and 1500 nmol/min/kg). Together with an increase in the plasma concentrations of trimethoprim, the CLR (mL/min/kg) of trimethoprim decreased to 25.9 ± 3.2, 13.5 ± 5.7, and 8.92 ± 1.50 at the respective rates. Trimethoprim decreased the CLR of rhodamine 123 in an infusion rate-dependent manner: 11.5 ± 1.3 (control), 5.17 ± 1.55, 1.31 ± 0.50, and 0.532 ± 0.180. These results suggest that Mate1 mediates the tubular secretion of trimethoprim, and at therapeutic doses, MATEs-mediated efflux can be saturated, and thereby, cause drug interactions with other MATE substrates. 相似文献
3.
教学与德育有机融会贯通,是当前教育领域的共识。医学本科生秉承"以德载医"的精神,肩负"治病救人"的重任,因此德育教育在整个医学教学中占有重要的地位。《医用有机化学》教材中含有丰富的德育内容,高校教师传授专业知识的同时,在教学过程中巧妙的穿插辩证唯物主义、爱国主义和社会责任感的思政教育,可以帮助学生们树立正确的世界观和人生观。文章以医用有机化学课程为例,主要从教师的自身道德素养、德育在教学过程中的具体实践和德育实施过程中需要注意的问题三方面进行阐述,充分将新时代新理念融入大纲、教案和课堂中,化"知识"为"智慧",变"文化"为"品格",充分发挥医用有机化学课程的德育功能。 相似文献
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5.
Stephen Hanessian 《ACS medicinal chemistry letters》2016,7(1):6-9
Current major advances in drug discovery
can be traced back to
pioneering contributions originating from academics over a century
ago. Living in a symbiotic yet noninvasive coexistence, the academic
community and the pharmaceutical industry have strived, each in their
own way, to develop the modern medicines that benefit humankind today.
The subject is presented from a historical and personal perspective. 相似文献
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8.
目的总结地高辛血药质量浓度监测方法,寻求最适的测定方法。方法对近年来国内外与地高辛监测相关的文献进行检索综述分析。结果地高辛血药浓度测定方法很多,常用方法主要有:FPIA、酶免疫分析法、RIA、CLIA、乳胶免疫抑制法、干化学法、HPLC法等。结论通过比较分析其中RIA、CLIA、EIA和HPLC MS 4种方法更好。 相似文献
9.
用有机锗(Ge-132)试验治疗荷移植肝癌小鼠。结果:De-132高剂量(12.5mg/次)治疗组的抑癌率为用31.0%,移植肝癌白细胞(WBC)浸润(+++)占72.7%、血清超氧化物歧化酶(SOD)活性为121Nu/ml,而生理盐水对照治疗组相应的后两项指标分别为用36.4%及81Nu/ml,两组比较有显著性差异(P<0.05);环磷酰胺(CTX)治疗组的抑癌率为37.0%,癌体WBC浸润(+++)为27.3%,血清SOD活性为102Nu/ml;ge-132高剂量与CTX2联合治疗组的抑癌率为45.0%,癌体WBC浸润(+++)为54.5%,血清SOD活性为142Nu/ml,两组比较,后二项指标有显著性差异(P<0.05)。由此提示Ge-132高剂量能明显增强荷移植肝癌小鼠的细胞免疫及血清SOD活性,并有一定的抗移植肝癌作用。 相似文献
10.
Occupational hydrocarbon exposure and chronic nephropathy 总被引:2,自引:0,他引:2
P. Hotz 《Toxicology》1994,90(3):163-283
This review aims at discussing the questions raised by the hydrocarbon-related chronic nephropathy and its possible consequence, the hydrocarbon-related chronic renal failure. It has been attempted to adopt the point of view of the clinician. Therefore, the most important part of the review is devoted to a presentation and an analysis of the available data on humans. The main features of the available studies on human subjects are presented, their conclusions discussed in the light of the possible methodological flaws, and practical conclusions drawn. After a discussion of the main difficulties encountered for selecting the suitable exposure indicator, the studies are discussed in order of decreasing quality of the study design (cohort, case-control, cross-sectional studies, and the case reports). It is concluded that a great deal of controversies about chronic hydrocarbon-related nephropathy is explained by differences in the study design and that hydrocarbon-induced nephropathy is probably more than a mere hypothesis, although a causal relationship has not yet been proven. Finally, some practical consequences for dealing with a hydrocarbon-exposed patient diagnosed with a kidney disease and the need for further research are discussed. 相似文献