Regular ArticleIdentification and Species Similarity of OATP Transporters Responsible for Hepatic Uptake of β-Lactam Antibiotics
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Predicting disruptions to drug pharmacokinetics and the risk of adverse drug reactions in non-alcoholic steatohepatitis patients
2023, Acta Pharmaceutica Sinica BCitation Excerpt :Based on these data, the dysfunction in metabolizing enzyme and transporter activities can impact the pharmacokinetics of other drugs eliminated through the same pathways and can be involved in the onset of ADRs. According to this hypothesis, we aimed to identify a list of sensitive drugs whose ADME kinetics could be disrupted (Table 337,48,80,96,101–103,114,134–136,152,154,288,292-586). We applied the same methodology as for Tables 1 and 2 to perform bibliographic research to identify the drugs that have been described as substrates for transporters or metabolizing enzymes modified in NASH.
Hepatic solute carrier transporters and drug therapy: Regulation of expression and impact of genetic variation
2022, Pharmacology and TherapeuticsInteraction of swine organic anion transporting polypeptide 1a2 with tetracycline, macrolide and β-lactam antibiotics
2019, Toxicology and Applied PharmacologyCitation Excerpt :Results of our current study seemed to suggest that sOatp1a2, which is dominantly expressed at the pig liver, may behave more similarly to human OATPs found in the hepatocytes. All three β-lactam antibiotics were found to be both inhibitors and substrates of sOatp1a2, a phenomenon that is similar to that observed in the human liver-specific transporter OATP1B3 (Nakakariya et al., 2008a) and the rat Oatp1a4, which was shown to be the predominant contributor to basolateral uptake of nafcillin by rat hepatocytes (Nakakariya et al., 2008b). All the tested β-lactam antibiotics exhibited similar IC50, though penicillin seemed to be a more potent substrate of sOatp1a2.
Evaluation of New Chemical Entities as Substrates of Liver Transporters in the Pharmaceutical Industry: Response to Regulatory Requirements and Future Steps
2017, Journal of Pharmaceutical SciencesCitation Excerpt :By using Xenopus oocytes–expressing OATPs, they demonstrated that all the 7 β-lactam antibiotics tested in the study were transported by both OATP1B3 and Oatp1a4; in addition, 4 were transported by OATP1B1 as well. A good correlation was observed between the ranked order of transporter activity of OATP1B3 and that of OATP1a4.18 Based on these reports, rat is deemed a useful animal species for the qualitative evaluation of NCEs.
The effects of dietary and herbal phytochemicals on drug transporters
2017, Advanced Drug Delivery ReviewsCitation Excerpt :Thus, EGCG might inhibit hepatic uptake of an OCT1 substrate (e.g., metformin, sumatriptan) and increase its plasma concentration in patients drinking green tea or taking herbal supplements containing a high dose of EGCG. OATP1B1 (LST1/OATPC/OATP-2/SLCO1B3) is a liver-specific transporter that mediates the uptake into the hepatocytes of a broad range of drugs, including statins (e.g., pravastatin [191], fluvastatin [192]), antibiotics (e.g., rifampicin [193], beta lactam antibiotics [194]), angiotension II receptor blockers (e.g., olmesartan [195], valsartan [196]), HIV protease inhibitors [197], fexofenadine [198], methotrexate [199] and SN-38 [200], as well as several endogenous substrates, such as bile salts, conjugated steroids, eicosanoids, thyroid hormones and coproporphyrins I and III [201,28,165,202–204]. Accumulating evidence suggests that genetic variants affecting OATP1B1 activity are important determinants of the hepatic clearance of its substrates [205–207].
Influence of peptide transporter 2 (PEPT2) on the distribution of cefadroxil in mouse brain: A microdialysis study
2017, Biochemical Pharmacology