Predicting disruptions to drug pharmacokinetics and the risk of adverse drug reactions in non-alcoholic steatohepatitis patients
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 ex...
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| Format: | Article |
| Language: | English |
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Elsevier
2023-01-01
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| Series: | Acta Pharmaceutica Sinica B |
| Subjects: | |
| Online Access: | http://www.sciencedirect.com/science/article/pii/S2211383522003690 |
| _version_ | 1811172036771315712 |
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| author | Solène Marie Kayla L. Frost Raymond K. Hau Lucy Martinez-Guerrero Jailyn M. Izu Cassandra M. Myers Stephen H. Wright Nathan J. Cherrington |
| author_facet | Solène Marie Kayla L. Frost Raymond K. Hau Lucy Martinez-Guerrero Jailyn M. Izu Cassandra M. Myers Stephen H. Wright Nathan J. Cherrington |
| author_sort | Solène Marie |
| collection | DOAJ |
| description | 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. |
| first_indexed | 2024-04-10T17:23:52Z |
| format | Article |
| id | doaj.art-8844d7a2d73949a28728c4480052e7fb |
| institution | Directory Open Access Journal |
| issn | 2211-3835 |
| language | English |
| last_indexed | 2024-04-10T17:23:52Z |
| publishDate | 2023-01-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Acta Pharmaceutica Sinica B |
| spelling | doaj.art-8844d7a2d73949a28728c4480052e7fb2023-02-05T04:16:01ZengElsevierActa Pharmaceutica Sinica B2211-38352023-01-01131128Predicting disruptions to drug pharmacokinetics and the risk of adverse drug reactions in non-alcoholic steatohepatitis patientsSolène Marie0Kayla L. Frost1Raymond K. Hau2Lucy Martinez-Guerrero3Jailyn M. Izu4Cassandra M. Myers5Stephen H. Wright6Nathan J. Cherrington7College of Pharmacy, Department of Pharmacology & Toxicology, University of Arizona, Tucson, AZ 85721, USACollege of Pharmacy, Department of Pharmacology & Toxicology, University of Arizona, Tucson, AZ 85721, USACollege of Pharmacy, Department of Pharmacology & Toxicology, University of Arizona, Tucson, AZ 85721, USACollege of Pharmacy, Department of Pharmacology & Toxicology, University of Arizona, Tucson, AZ 85721, USACollege of Pharmacy, Department of Pharmacology & Toxicology, University of Arizona, Tucson, AZ 85721, USACollege of Pharmacy, Department of Pharmacology & Toxicology, University of Arizona, Tucson, AZ 85721, USACollege of Medicine, Department of Physiology, University of Arizona, Tucson, AZ 85724, USACollege of Pharmacy, Department of Pharmacology & Toxicology, University of Arizona, Tucson, AZ 85721, USA; Corresponding author. Tel.: +1 520 6260219; fax: +1 520 6266944.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.http://www.sciencedirect.com/science/article/pii/S2211383522003690Non-alcoholic steatohepatitisHepatic eliminationTransporterEnzymePharmacokineticsDrug–drug interaction |
| spellingShingle | Solène Marie Kayla L. Frost Raymond K. Hau Lucy Martinez-Guerrero Jailyn M. Izu Cassandra M. Myers Stephen H. Wright Nathan J. Cherrington Predicting disruptions to drug pharmacokinetics and the risk of adverse drug reactions in non-alcoholic steatohepatitis patients Acta Pharmaceutica Sinica B Non-alcoholic steatohepatitis Hepatic elimination Transporter Enzyme Pharmacokinetics Drug–drug interaction |
| title | Predicting disruptions to drug pharmacokinetics and the risk of adverse drug reactions in non-alcoholic steatohepatitis patients |
| title_full | Predicting disruptions to drug pharmacokinetics and the risk of adverse drug reactions in non-alcoholic steatohepatitis patients |
| title_fullStr | Predicting disruptions to drug pharmacokinetics and the risk of adverse drug reactions in non-alcoholic steatohepatitis patients |
| title_full_unstemmed | Predicting disruptions to drug pharmacokinetics and the risk of adverse drug reactions in non-alcoholic steatohepatitis patients |
| title_short | Predicting disruptions to drug pharmacokinetics and the risk of adverse drug reactions in non-alcoholic steatohepatitis patients |
| title_sort | predicting disruptions to drug pharmacokinetics and the risk of adverse drug reactions in non alcoholic steatohepatitis patients |
| topic | Non-alcoholic steatohepatitis Hepatic elimination Transporter Enzyme Pharmacokinetics Drug–drug interaction |
| url | http://www.sciencedirect.com/science/article/pii/S2211383522003690 |
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