ArticleThe Journal of pharmacology and experimental therapeutics2014
Experimental nonalcoholic steatohepatitis increases exposure to simvastatin hydroxy acid by decreasing hepatic organic anion transporting polypeptide expression.
Article in The Journal of pharmacology and experimental therapeutics, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 22 papers.
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Who cites it
22 citing papers in PubMed, 47 citations in OpenAlex.
- Resolution of non-alcoholic steatohepatitis by rosuvastatin monotherapy in patients with metabolic syndrome.World journal of gastroenterology · 2015Trial
- Article
- Considerations for Physiologically Based Modeling in Liver Disease: From Nonalcoholic Fatty Liver (NAFL) to Nonalcoholic Steatohepatitis (NASH).Clinical pharmacology and therapeutics · 2023Review
- Evodiamine decreased the systemic exposure of pravastatin in non-alcoholic steatohepatitis rats due to the up-regulation of hepatic OATPs.Pharmaceutical biology · 2022Article
- OATP1B3 Expression and Function is Modulated by Coexpression with OCT1, OATP1B1, and NTCP.Drug metabolism and disposition: the biological fate of chemicals · 2020Article
- Impact of SLCO1B1 Genetic Variation on Rosuvastatin Systemic Exposure in Pediatric Hypercholesterolemia.Clinical and translational science · 2020Observational
- A Pharmacokinetic Natural Product-Disease-Drug Interaction: A Double Hit of Silymarin and Nonalcoholic Steatohepatitis on Hepatic Transporters in a Rat Model.The Journal of pharmacology and experimental therapeutics · 2019Article
- Sub-Chronic Microcystin-LR Liver Toxicity in Preexisting Diet-Induced Nonalcoholic Steatohepatitis in Rats.Toxins · 2019Article
- Nonalcoholic fatty liver disease alters microcystin-LR toxicokinetics and acute toxicity.Toxicon : official journal of the International Society on Toxinology · 2019Article
- Asking the Right Questions With Animal Models: Methionine- and Choline-Deficient Model in Predicting Adverse Drug Reactions in Human NASH.Toxicological sciences : an official journal of the Society of Toxicology · 2018Article
- Effect of Liver Disease on Hepatic Transporter Expression and Function.Journal of pharmaceutical sciences · 2017Review
- Impaired N-linked glycosylation of uptake and efflux transporters in human non-alcoholic fatty liver disease.Liver international : official journal of the International Association for the Study of the Liver · 2017Article
- Population Pharmacokinetics of Morphine in Patients With Nonalcoholic Steatohepatitis (NASH) and Healthy Adults.CPT: pharmacometrics & systems pharmacology · 2017Article
- Effect of nonalcoholic steatohepatitis on renal filtration and secretion of adefovir.Biochemical pharmacology · 2016Article
- Biliary Elimination of Pemetrexed Is Dependent on Mrp2 in Rats: Potential Mechanism of Variable Response in Nonalcoholic Steatohepatitis.The Journal of pharmacology and experimental therapeutics · 2016Article
- Altered Hepatic Transport by Fetal Arsenite Exposure in Diet-Induced Fatty Liver Disease.Journal of biochemical and molecular toxicology · 2016Article
- Article
- Nonalcoholic steatohepatitis in precision medicine: Unraveling the factors that contribute to individual variability.Pharmacology & therapeutics · 2015Review
- Altered morphine glucuronide and bile acid disposition in patients with nonalcoholic steatohepatitis.Clinical pharmacology and therapeutics · 2015Article
- Mechanistic basis of altered morphine disposition in nonalcoholic steatohepatitis.The Journal of pharmacology and experimental therapeutics · 2015Article
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Authors and funding
5 authors at 1 institution in 1 country.
Funding
Abstract
Simvastatin (SIM)-induced myopathy is a dose-dependent adverse drug reaction (ADR) that has been reported to occur in 18.2% of patients receiving a 40- to 80-mg dose. The pharmacokinetics of SIM hydroxy acid (SIMA), the bioactive form of SIM, and the occurrence of SIM-induced myopathy are linked to the function of the organic anion transporting polypeptide (Oatp) hepatic uptake transporters. Genetic polymorphisms in SLCO1B1, the gene for human hepatic OATP1B1, cause decreased elimination of SIMA and increased risk of developing myopathy. Nonalcoholic steatohepatitis (NASH) is the most severe form of nonalcoholic fatty liver disease, and is known to alter drug transporter expression and drug disposition. The purpose of this study was to assess the metabolism and disposition of SIM in a diet-induced rodent model of NASH. Rats were fed a methionine- and choline-deficient diet for 8 weeks to induce NASH and SIM was administered intravenously. Diet-induced NASH caused increased plasma retention and decreased biliary excretion of SIMA due to decreased protein expression of multiple hepatic Oatps. SIM exhibited increased volume of distribution in NASH as evidenced by increased muscle, decreased plasma, and no change in biliary concentrations. Although Cyp3a and Cyp2c11 proteins were decreased in NASH, no alterations in SIM metabolism were observed. These data, in conjunction with our previous data showing that human NASH causes a coordinated downregulation of hepatic uptake transporters, suggest that NASH-mediated transporter regulation may play a role in altered SIMA disposition and the occurrence of myopathy.
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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.