Predicting disruptions to drug pharmacokinetics and the risk of adverse drug reactions in non-alcoholic steatohepatitis patients

[11C]glyburide PET imaging for quantitative determination of the importance of Organic Anion-Transporting Polypeptide transporter function in the human liver and whole-body

“…However, contribution of other transporters in the liver uptake of [ 11 C]glyburide cannot be excluded. To the best of our knowledge, glyburide has not been reported as a substrate of organic cation transporter 1 (OCT1), another important influx transporter expressed at the sinusoidal pole of hepatocytes [38,39]. In our study, almost complete inhibition of the liver uptake of [ 11 C] glyburide was achieved using rifampicin which may inhibit multiple hepatocyte transporters including OATPs but does not inhibit OCT1 [40,41].…”

“…They also suggested that liver uptake of metabolites is ~10-fold lower compared with parent glyburide, thus supporting suitable radiochemical purity of the PET signal for [ 11 C]glyburide in the liver [26]. A large and consistent body of research suggests that the liver uptake of glyburide is predominantly mediated by OATP transporter(s) [26,38,39]. However, contribution of other transporters in the liver uptake of [ 11 C]glyburide cannot be excluded.…”

The deubiquitinating enzyme 13 retards non-alcoholic steatohepatitis via blocking inactive rhomboid protein 2-dependent pathway

“…As it is, a number of molecular targets and potential clinical application drugs for NAFLD/NASH treatment have been extensively studied 9 , 10 , 11 . Recently, increasing evidence revealed that IRHOM2 plays a critical role in the progression of hepatosteatosis, including the regulation of liver inflammation, lipid metabolism and glucose homeostasis 12 , 13 .…”

“…Recently, it is even more regrettable that a series of potential drugs for the treatment of NASH ( e . g ., selonsertib, elafibranor and GR-MD-02) have failed to achieve expected therapeutic efficacy because they did not meet the expected clinical endpoint 9 , 10 , 11 . The failure of these promising clinical treatment drugs further proved that the pathological process of NASH involving a complicated molecular mechanism and may also track with many physiological and metabolic processes.…”

Neues zur Fettleber: Nomenklatur, Screening-Empfehlungen, Therapiebemühungen und andere klinisch relevante Aspekte

“…Vor allem CYP3A4, das wichtigste mikrosomale Enzym in der Leber für die Metabolisierung zahlreicher Medikamente, ist deutlich reduziert [22]. Jüngste Schätzungen gehen von pharmakokinetisch relevanten Änderungen des Metabolismus in der Fettleber bei über 70 medizinisch wichtigen Substanzen aus [23], klinische Daten fehlen aber vielfach. Die Entwicklung eines klinischen Bewusstseins für diese Problematik ist bei der Zunahme der Fettleber in der (häufig multimorbiden) Population…”