Prediction of drug-induced kidney injury in drug discovery

Drug Metab Rev. 2021 May 17:1-11. doi: 10.1080/03602532.2021.1922436. Online ahead of print.ABSTRACTDrug induced kidney injury is one of the leading causes of failure of drug development programs in the clinic. Early prediction of renal toxicity potential of drugs is crucial to the success of drug candidates in the clinic. The dynamic nature of the functioning of the kidney and the presence of drug uptake proteins introduce additional challenges in the prediction of renal injury caused by drugs. Renal injury due to drugs can be caused by a wide variety of mechanisms and can be broadly classified as toxic or obstructive. Several biomarkers are available for in vitro and in vivo detection of renal injury. In vitro static and dynamic (microfluidic) cellular models and preclinical models can provide valuable information regarding the toxicity potential of drugs. Differences in pharmacology and subsequent disconnect in biomarker response, differences in the expression of transporter and enzyme proteins between in vitro to in vivo systems and between preclinical species and humans are some of the limitations of current experimental models. The progress in microfluidic (kidney-on-chip) platforms in combination with the ability of 3-dimensional cell culture can help in addressing some of these issues in the future. Finally, newer in silico and computational techniques like physiologically based pharmacokinetic modeling and machine learning have demonstrated potential in assisting pre...
Source: Drug Metabolism Reviews - Category: Drugs & Pharmacology Authors: Source Type: research

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CONCLUSION: Prevalence of antibiotic use was high not only versus other hospitals in the region but globally including Africa, coupled with significant evidence of sub-optimal prescribing. Swift action is needed to improve future prescribing to reduce AMR. One or two areas should initially be targeted for quality improvement including development of local guidelines, documentation of antibiotic indications and/or stop/review dates. PMID: 33034234 [PubMed - as supplied by publisher]
Source: Expert Review of Anti-Infective Therapy - Category: Infectious Diseases Tags: Expert Rev Anti Infect Ther Source Type: research
Authors: Rombauts A, Abelenda-Alonso G, Cuervo G, Gudiol C, Carratalà J Abstract INTRODUCTION: Despite adequate antibiotic coverage, community-acquired pneumonia (CAP) remains a leading cause of hospitalization and mortality worldwide. It induces both a local pulmonary and a systemic inflammatory response, particularly significant in severe cases. The intensity of the dysregulated host response varies from patient to patient and has a negative impact on survival and other outcomes. AREAS COVERED: This comprehensive review summarizes the pathophysiological aspects of the inflammatory response in CAP, brie...
Source: Expert Review of Anti-Infective Therapy - Category: Infectious Diseases Tags: Expert Rev Anti Infect Ther Source Type: research
Authors: Hammerschlag MR, Sharma R Abstract INTRODUCTION: Azithromycin was recommended as the first-line therapeutic regimen for treatment of genital infections in men and women by the Centers for Disease Control in 1998. A series of studies of azithromycin for treatment of rectal chlamydial infection in men who have sex with men (MSM) found that azithromycin was significantly less effective than doxycycline. AREAS COVERED: Literature on treatment of rectal C. trachomatis from 2000 through May 2020 was searched using PubMed. Retrospective and observational studies were identified documenting the frequency and t...
Source: Expert Review of Anti-Infective Therapy - Category: Infectious Diseases Tags: Expert Rev Anti Infect Ther Source Type: research
Authors: Reissier S, Cattoir V Abstract INTRODUCTION: Streptogramins (pristinamycin and quinupristin-dalfopristin) can be interesting options for the treatment of infections due to Gram-positive cocci, especially multidrug-resistant isolates. AREAS COVERED: This review provides an updated overview on structural and activity characteristics, mechanisms of action and resistance, pharmacokinetic/pharmacodynamic and clinical use of streptogramins. EXPERT OPINION: The streptogramin antibiotics act by inhibition of the bacterial protein synthesis. They are composed of two chemically distinct compounds, namely typ...
Source: Expert Review of Anti-Infective Therapy - Category: Infectious Diseases Tags: Expert Rev Anti Infect Ther Source Type: research
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Source: Journal of Hazardous Materials - Category: Environmental Health Source Type: research
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Source: Journal of Hazardous Materials - Category: Environmental Health Source Type: research
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Source: Journal of Hazardous Materials - Category: Environmental Health Source Type: research
Publication date: 15 February 2021Source: Journal of Hazardous Materials, Volume 404, Part AAuthor(s): Cheng Han, Yinping Zhang, Marc Redmile-Gordon, Huan Deng, Zhenggui Gu, Qiguo Zhao, Fang Wang
Source: Journal of Hazardous Materials - Category: Environmental Health Source Type: research
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Source: Journal of Hazardous Materials - Category: Environmental Health Source Type: research
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