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Predicting disruptions to drug pharmacokinetics and the risk of adverse drug reactions in nonalcoholic steatohepatitis patients

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Acta Pharmaceutica Sinica B 2023年第1期13卷 1-28页

作者： Solène Marie Kayla L.Frost Raymond K.Hau Lucy Martinez-Guerrero Jailyn M.Izu Cassandra M.Myers Stephen H.Wright Nathan J.Cherrington College of Pharmacy Department of Pharmacology&ToxicologyUniversity of ArizonaTucsonAZ 85721USA College of Medicine Department of PhysiologyUniversity of ArizonaTucsonAZ 85724USA

The liver plays a central role in the pharmacokinetics of drugs through drug metabolizing enzymes and ***-alcoholic steatohepatitis(NASH)causes disease-specific alterations to the absorption,distribution,metabolism,and excretion(ADME)processes,including a decrease in protein expression of basolateral uptake transporters,an increase in efflux transporters,and modifications to enzyme *** can result in increased drug exposure and adverse drug reactions(ADRs).Our goal was to predict drugs that pose increased risks for ADRs in NASH *** research identified 71 drugs with reported ADRs in patients with liver disease,mainly non-alcoholic fatty liver disease(NAFLD),54 of which are known substrates of transporters and/or metabolizing *** NASH is the progressive form of NAFLD but is most frequently undiagnosed,we identified other drugs at risk based on NASH-specific alterations to ADME ***,we present another list of 71 drugs at risk of pharmacokinetic disruption in NASH,based on their transport and/or metabolism *** encompasses drugs from various pharmacological classes for which ADRs may occur when used in NASH patients,especially when eliminated through multiple pathways altered by the ***,these results may inform clinicians regarding the selection of drugs for use in NASH patients.

关键词： Non-alcoholic steatohepatitis hepatic elimination Transporter Enzyme Pharmacokinetics Drug-drug interaction Liver Adverse drug reaction

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