TY - JOUR
T1 - Predicting disruptions to drug pharmacokinetics and the risk of adverse drug reactions in non-alcoholic steatohepatitis patients
AU - Marie, Solène
AU - Frost, Kayla L.
AU - Hau, Raymond K.
AU - Martinez-Guerrero, Lucy
AU - Izu, Jailyn M.
AU - Myers, Cassandra M.
AU - Wright, Stephen H.
AU - Cherrington, Nathan J.
N1 - Funding Information: This study was supported by National Institutes of Health (R01ES028668 and P30ES006694, USA ). Solène Marie was supported by a Fulbright Grant from the Franco-American Commission for Educational Exchange and by a fellowship from the L'Oréal- UNESCO Foundation for Women in Science ( France ). The authors would like to thank the University of Alberta (Canada) and their partners for creating and funding the online free-to-access database DrugBank ( https://go.drugbank.com/ ) which was used for this bibliographic research. Funding Information: This study was supported by National Institutes of Health (R01ES028668 and P30ES006694, USA). Solène Marie was supported by a Fulbright Grant from the Franco-American Commission for Educational Exchange and by a fellowship from the L'Oréal-UNESCO Foundation for Women in Science (France). The authors would like to thank the University of Alberta (Canada) and their partners for creating and funding the online free-to-access database DrugBank (https://go.drugbank.com/) which was used for this bibliographic research. Publisher Copyright: © 2023 Chinese Pharmaceutical Association and Institute of Materia Medica, Chinese Academy of Medical Sciences
PY - 2023/1
Y1 - 2023/1
N2 - The liver plays a central role in the pharmacokinetics of drugs through drug metabolizing enzymes and transporters. Non-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 activity. This 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 patients. Bibliographic 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 enzymes. Since 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 processes. Here, we present another list of 71 drugs at risk of pharmacokinetic disruption in NASH, based on their transport and/or metabolism processes. It 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 disease. Therefore, these results may inform clinicians regarding the selection of drugs for use in NASH patients.
AB - The liver plays a central role in the pharmacokinetics of drugs through drug metabolizing enzymes and transporters. Non-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 activity. This 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 patients. Bibliographic 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 enzymes. Since 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 processes. Here, we present another list of 71 drugs at risk of pharmacokinetic disruption in NASH, based on their transport and/or metabolism processes. It 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 disease. Therefore, these results may inform clinicians regarding the selection of drugs for use in NASH patients.
KW - Adverse drug reaction
KW - Drug–drug interaction
KW - Enzyme
KW - Hepatic elimination
KW - Liver
KW - Non-alcoholic steatohepatitis
KW - Pharmacokinetics
KW - Transporter
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U2 - 10.1016/j.apsb.2022.08.018
DO - 10.1016/j.apsb.2022.08.018
M3 - Review article
SN - 2211-3835
VL - 13
SP - 1
EP - 28
JO - Acta Pharmaceutica Sinica B
JF - Acta Pharmaceutica Sinica B
IS - 1
ER -