ArticleDrug metabolism and disposition: the biological fate of chemicals2016
Transporter Expression in Liver Tissue from Subjects with Alcoholic or Hepatitis C Cirrhosis Quantified by Targeted Quantitative Proteomics.
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Article in Drug metabolism and disposition: the biological fate of chemicals, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 53 papers, 1 of them a synthesis that pooled it.
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53citing papers in PubMed, 1 pooled it
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Who cites it
53 citing papers in PubMed, 1 synthesis or guideline pooled it, 118 citations in OpenAlex.
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- Raltegravir pharmacokinetics before and during treatment with ombitasvir, paritaprevir/ritonavir plus dasabuvir in adults with human immunodeficiency virus-1 and hepatitis C virus coinfection: AIDS Clinical Trials Group sub-study A5334s.British journal of clinical pharmacology · 2020Trial
- Hepatic drug transporters in pharmacotherapy: mechanisms, therapeutic targeting, and clinical translation.Naunyn-Schmiedeberg's archives of pharmacology · 2026Review
- HBV/HCV coinfection and anti-tuberculosis drug-induced liver injury: from risk assessment and exploration of mechanisms to preventive considerations.European journal of clinical microbiology & infectious diseases : official publication of the European Society of Clinical Microbiology · 2026Review
- Ethanol as a Modifier of Drug Toxicity in Humans: Pathways of Toxicity and Organ-Level Consequences.International journal of molecular sciences · 2026Review
- Comprehensive Pathophysiology Repository for PBPK Modeling in Liver Cirrhosis: Quantifying Continuous Disease Progression and Population Variability.CPT: pharmacometrics & systems pharmacology · 2026Article
- Using Physiologically Based Pharmacokinetic Modeling and Simulations to Predict Antihypertensive Drug Doses in Cirrhotic Patients.Journal of clinical pharmacology · 2026Article
- Rosuvastatin PBPK Modeling: Incorporating Liver Concentrations and Effects of Ethnicity, Genetic Polymorphisms, Lactone Formation, DDI and Pregnancy.CPT: pharmacometrics & systems pharmacology · 2025Article
- Exploratory Study of Sex Differences in P-Glycoprotein Function at the Blood-Brain Barrier.Clinical and translational science · 2025Article
- Drug-Drug Interactions Between HIV Antivirals and Concomitant Drugs in HIV Patients: What We Know and What We Need to Know.Pharmaceutics · 2024Review
- Liver Fibrosis Stages Affect Organic Cation Transporter 1/2 Activities in Hepatitis C Virus-Infected Patients.Pharmaceuticals (Basel, Switzerland) · 2024Article
- Toward improved predictions of pharmacokinetics of transported drugs in hepatic impairment: Insights from the extended clearance model.CPT: pharmacometrics & systems pharmacology · 2024Article
- The Role of CYPs and Transporters in the Biotransformation and Transport of the Anti-hepatitis C Antiviral Agents Asunaprevir, Daclatasvir, and Beclabuvir: Impact of Liver Disease, Race and Drug-drug Interactions on Safety and Efficacy.Current drug metabolism · 2024Review
- Evaluation of liver function using Gd-EOB-DTPA-enhanced MRI with T1 mapping.BMC medical imaging · 2023Article
- Assessing Liver Fibrosis Using 2D-SWE Liver Ultrasound Elastography and Dynamic Liver Scintigraphy with 99mTc-mebrofenin: A Comparative Prospective Single-Center Study.Medicina (Kaunas, Lithuania) · 2023Article
- Predicting changes in the pharmacokinetics of CYP3A-metabolized drugs in hepatic impairment and insights into factors driving these changes.CPT: pharmacometrics & systems pharmacology · 2023Article
- Renal Transporter Alterations in Patients with Chronic Liver Diseases: Nonalcoholic Steatohepatitis, Alcohol-Associated, Viral Hepatitis, and Alcohol-Viral Combination.Drug metabolism and disposition: the biological fate of chemicals · 2023Article
- Predicting disruptions to drug pharmacokinetics and the risk of adverse drug reactions in non-alcoholic steatohepatitis patients.Acta pharmaceutica Sinica. B · 2023Review
- Human Hepatic Transporter Signature Peptides for Quantitative Targeted Absolute Proteomics: Selection, Digestion Efficiency, and Peptide Stability.Pharmaceutical research · 2022Article
- Effect of alcohol exposure on the efficacy and safety of tenofovir alafenamide fumarate, a major medicine against human immunodeficiency virus.Biochemical pharmacology · 2022Article
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Authors and funding
16 authors at 6 institutions in 2 countries.
Li WangDepartment of Pharmaceutics, University of Washington, Seattle, Washington (L.W., C.C., E.J.K., J.D.U.); Pharmacokinetics, Pharmacodynamics, and Drug Metabolism, Merck & Co., Rahway, New Jersey (X.C.); Departments of Clinical Pharmacology and Drug Metabolism and Pharmacokinetics, Gilead Sciences, Inc., Foster City, California (A.S.R., A.M.); Drug Metabolism and Pharmacokinetics, Genentech, South San Francisco, California (L.S., C.E.C.A.H.); Preclinical PK and In Vitro ADME, Biogen, Cambridge, Massachusetts (G.X.); Pharmacokinetics, Pharmacodynamics, and Drug Metabolism, Ardea Biosciences, Inc., San Diego, California (C.L.); Pharmaceutical Candidate Optimization, Bristol-Myers Squibb Company, Princeton, New Jersey (Y.L.,W.H.); Takeda Pharmaceuticals International Co., Cambridge, Massachusetts (M.L.); Pharmacokinetics, Pharmacodynamics, and Drug Metabolism, Merck & Co., Kenilworth, New Jersey (R.E.); Department of Surgery, University of Kansas Medical Center, Kansas City, Kansas (S.C.K.).
Carol CollinsDepartment of Pharmaceutics, University of Washington, Seattle, Washington (L.W., C.C., E.J.K., J.D.U.); Pharmacokinetics, Pharmacodynamics, and Drug Metabolism, Merck & Co., Rahway, New Jersey (X.C.); Departments of Clinical Pharmacology and Drug Metabolism and Pharmacokinetics, Gilead Sciences, Inc., Foster City, California (A.S.R., A.M.); Drug Metabolism and Pharmacokinetics, Genentech, South San Francisco, California (L.S., C.E.C.A.H.); Preclinical PK and In Vitro ADME, Biogen, Cambridge, Massachusetts (G.X.); Pharmacokinetics, Pharmacodynamics, and Drug Metabolism, Ardea Biosciences, Inc., San Diego, California (C.L.); Pharmaceutical Candidate Optimization, Bristol-Myers Squibb Company, Princeton, New Jersey (Y.L.,W.H.); Takeda Pharmaceuticals International Co., Cambridge, Massachusetts (M.L.); Pharmacokinetics, Pharmacodynamics, and Drug Metabolism, Merck & Co., Kenilworth, New Jersey (R.E.); Department of Surgery, University of Kansas Medical Center, Kansas City, Kansas (S.C.K.).
Edward J KellyDepartment of Pharmaceutics, University of Washington, Seattle, Washington (L.W., C.C., E.J.K., J.D.U.); Pharmacokinetics, Pharmacodynamics, and Drug Metabolism, Merck & Co., Rahway, New Jersey (X.C.); Departments of Clinical Pharmacology and Drug Metabolism and Pharmacokinetics, Gilead Sciences, Inc., Foster City, California (A.S.R., A.M.); Drug Metabolism and Pharmacokinetics, Genentech, South San Francisco, California (L.S., C.E.C.A.H.); Preclinical PK and In Vitro ADME, Biogen, Cambridge, Massachusetts (G.X.); Pharmacokinetics, Pharmacodynamics, and Drug Metabolism, Ardea Biosciences, Inc., San Diego, California (C.L.); Pharmaceutical Candidate Optimization, Bristol-Myers Squibb Company, Princeton, New Jersey (Y.L.,W.H.); Takeda Pharmaceuticals International Co., Cambridge, Massachusetts (M.L.); Pharmacokinetics, Pharmacodynamics, and Drug Metabolism, Merck & Co., Kenilworth, New Jersey (R.E.); Department of Surgery, University of Kansas Medical Center, Kansas City, Kansas (S.C.K.).
Xiaoyan ChuDepartment of Pharmaceutics, University of Washington, Seattle, Washington (L.W., C.C., E.J.K., J.D.U.); Pharmacokinetics, Pharmacodynamics, and Drug Metabolism, Merck & Co., Rahway, New Jersey (X.C.); Departments of Clinical Pharmacology and Drug Metabolism and Pharmacokinetics, Gilead Sciences, Inc., Foster City, California (A.S.R., A.M.); Drug Metabolism and Pharmacokinetics, Genentech, South San Francisco, California (L.S., C.E.C.A.H.); Preclinical PK and In Vitro ADME, Biogen, Cambridge, Massachusetts (G.X.); Pharmacokinetics, Pharmacodynamics, and Drug Metabolism, Ardea Biosciences, Inc., San Diego, California (C.L.); Pharmaceutical Candidate Optimization, Bristol-Myers Squibb Company, Princeton, New Jersey (Y.L.,W.H.); Takeda Pharmaceuticals International Co., Cambridge, Massachusetts (M.L.); Pharmacokinetics, Pharmacodynamics, and Drug Metabolism, Merck & Co., Kenilworth, New Jersey (R.E.); Department of Surgery, University of Kansas Medical Center, Kansas City, Kansas (S.C.K.).
Adrian S RayDepartment of Pharmaceutics, University of Washington, Seattle, Washington (L.W., C.C., E.J.K., J.D.U.); Pharmacokinetics, Pharmacodynamics, and Drug Metabolism, Merck & Co., Rahway, New Jersey (X.C.); Departments of Clinical Pharmacology and Drug Metabolism and Pharmacokinetics, Gilead Sciences, Inc., Foster City, California (A.S.R., A.M.); Drug Metabolism and Pharmacokinetics, Genentech, South San Francisco, California (L.S., C.E.C.A.H.); Preclinical PK and In Vitro ADME, Biogen, Cambridge, Massachusetts (G.X.); Pharmacokinetics, Pharmacodynamics, and Drug Metabolism, Ardea Biosciences, Inc., San Diego, California (C.L.); Pharmaceutical Candidate Optimization, Bristol-Myers Squibb Company, Princeton, New Jersey (Y.L.,W.H.); Takeda Pharmaceuticals International Co., Cambridge, Massachusetts (M.L.); Pharmacokinetics, Pharmacodynamics, and Drug Metabolism, Merck & Co., Kenilworth, New Jersey (R.E.); Department of Surgery, University of Kansas Medical Center, Kansas City, Kansas (S.C.K.).
Laurent SalphatiDepartment of Pharmaceutics, University of Washington, Seattle, Washington (L.W., C.C., E.J.K., J.D.U.); Pharmacokinetics, Pharmacodynamics, and Drug Metabolism, Merck & Co., Rahway, New Jersey (X.C.); Departments of Clinical Pharmacology and Drug Metabolism and Pharmacokinetics, Gilead Sciences, Inc., Foster City, California (A.S.R., A.M.); Drug Metabolism and Pharmacokinetics, Genentech, South San Francisco, California (L.S., C.E.C.A.H.); Preclinical PK and In Vitro ADME, Biogen, Cambridge, Massachusetts (G.X.); Pharmacokinetics, Pharmacodynamics, and Drug Metabolism, Ardea Biosciences, Inc., San Diego, California (C.L.); Pharmaceutical Candidate Optimization, Bristol-Myers Squibb Company, Princeton, New Jersey (Y.L.,W.H.); Takeda Pharmaceuticals International Co., Cambridge, Massachusetts (M.L.); Pharmacokinetics, Pharmacodynamics, and Drug Metabolism, Merck & Co., Kenilworth, New Jersey (R.E.); Department of Surgery, University of Kansas Medical Center, Kansas City, Kansas (S.C.K.).
Guangqing XiaoDepartment of Pharmaceutics, University of Washington, Seattle, Washington (L.W., C.C., E.J.K., J.D.U.); Pharmacokinetics, Pharmacodynamics, and Drug Metabolism, Merck & Co., Rahway, New Jersey (X.C.); Departments of Clinical Pharmacology and Drug Metabolism and Pharmacokinetics, Gilead Sciences, Inc., Foster City, California (A.S.R., A.M.); Drug Metabolism and Pharmacokinetics, Genentech, South San Francisco, California (L.S., C.E.C.A.H.); Preclinical PK and In Vitro ADME, Biogen, Cambridge, Massachusetts (G.X.); Pharmacokinetics, Pharmacodynamics, and Drug Metabolism, Ardea Biosciences, Inc., San Diego, California (C.L.); Pharmaceutical Candidate Optimization, Bristol-Myers Squibb Company, Princeton, New Jersey (Y.L.,W.H.); Takeda Pharmaceuticals International Co., Cambridge, Massachusetts (M.L.); Pharmacokinetics, Pharmacodynamics, and Drug Metabolism, Merck & Co., Kenilworth, New Jersey (R.E.); Department of Surgery, University of Kansas Medical Center, Kansas City, Kansas (S.C.K.).
Caroline LeeDepartment of Pharmaceutics, University of Washington, Seattle, Washington (L.W., C.C., E.J.K., J.D.U.); Pharmacokinetics, Pharmacodynamics, and Drug Metabolism, Merck & Co., Rahway, New Jersey (X.C.); Departments of Clinical Pharmacology and Drug Metabolism and Pharmacokinetics, Gilead Sciences, Inc., Foster City, California (A.S.R., A.M.); Drug Metabolism and Pharmacokinetics, Genentech, South San Francisco, California (L.S., C.E.C.A.H.); Preclinical PK and In Vitro ADME, Biogen, Cambridge, Massachusetts (G.X.); Pharmacokinetics, Pharmacodynamics, and Drug Metabolism, Ardea Biosciences, Inc., San Diego, California (C.L.); Pharmaceutical Candidate Optimization, Bristol-Myers Squibb Company, Princeton, New Jersey (Y.L.,W.H.); Takeda Pharmaceuticals International Co., Cambridge, Massachusetts (M.L.); Pharmacokinetics, Pharmacodynamics, and Drug Metabolism, Merck & Co., Kenilworth, New Jersey (R.E.); Department of Surgery, University of Kansas Medical Center, Kansas City, Kansas (S.C.K.).
Yurong LaiDepartment of Pharmaceutics, University of Washington, Seattle, Washington (L.W., C.C., E.J.K., J.D.U.); Pharmacokinetics, Pharmacodynamics, and Drug Metabolism, Merck & Co., Rahway, New Jersey (X.C.); Departments of Clinical Pharmacology and Drug Metabolism and Pharmacokinetics, Gilead Sciences, Inc., Foster City, California (A.S.R., A.M.); Drug Metabolism and Pharmacokinetics, Genentech, South San Francisco, California (L.S., C.E.C.A.H.); Preclinical PK and In Vitro ADME, Biogen, Cambridge, Massachusetts (G.X.); Pharmacokinetics, Pharmacodynamics, and Drug Metabolism, Ardea Biosciences, Inc., San Diego, California (C.L.); Pharmaceutical Candidate Optimization, Bristol-Myers Squibb Company, Princeton, New Jersey (Y.L.,W.H.); Takeda Pharmaceuticals International Co., Cambridge, Massachusetts (M.L.); Pharmacokinetics, Pharmacodynamics, and Drug Metabolism, Merck & Co., Kenilworth, New Jersey (R.E.); Department of Surgery, University of Kansas Medical Center, Kansas City, Kansas (S.C.K.).
Mingxiang LiaoDepartment of Pharmaceutics, University of Washington, Seattle, Washington (L.W., C.C., E.J.K., J.D.U.); Pharmacokinetics, Pharmacodynamics, and Drug Metabolism, Merck & Co., Rahway, New Jersey (X.C.); Departments of Clinical Pharmacology and Drug Metabolism and Pharmacokinetics, Gilead Sciences, Inc., Foster City, California (A.S.R., A.M.); Drug Metabolism and Pharmacokinetics, Genentech, South San Francisco, California (L.S., C.E.C.A.H.); Preclinical PK and In Vitro ADME, Biogen, Cambridge, Massachusetts (G.X.); Pharmacokinetics, Pharmacodynamics, and Drug Metabolism, Ardea Biosciences, Inc., San Diego, California (C.L.); Pharmaceutical Candidate Optimization, Bristol-Myers Squibb Company, Princeton, New Jersey (Y.L.,W.H.); Takeda Pharmaceuticals International Co., Cambridge, Massachusetts (M.L.); Pharmacokinetics, Pharmacodynamics, and Drug Metabolism, Merck & Co., Kenilworth, New Jersey (R.E.); Department of Surgery, University of Kansas Medical Center, Kansas City, Kansas (S.C.K.).
Anita MathiasDepartment of Pharmaceutics, University of Washington, Seattle, Washington (L.W., C.C., E.J.K., J.D.U.); Pharmacokinetics, Pharmacodynamics, and Drug Metabolism, Merck & Co., Rahway, New Jersey (X.C.); Departments of Clinical Pharmacology and Drug Metabolism and Pharmacokinetics, Gilead Sciences, Inc., Foster City, California (A.S.R., A.M.); Drug Metabolism and Pharmacokinetics, Genentech, South San Francisco, California (L.S., C.E.C.A.H.); Preclinical PK and In Vitro ADME, Biogen, Cambridge, Massachusetts (G.X.); Pharmacokinetics, Pharmacodynamics, and Drug Metabolism, Ardea Biosciences, Inc., San Diego, California (C.L.); Pharmaceutical Candidate Optimization, Bristol-Myers Squibb Company, Princeton, New Jersey (Y.L.,W.H.); Takeda Pharmaceuticals International Co., Cambridge, Massachusetts (M.L.); Pharmacokinetics, Pharmacodynamics, and Drug Metabolism, Merck & Co., Kenilworth, New Jersey (R.E.); Department of Surgery, University of Kansas Medical Center, Kansas City, Kansas (S.C.K.).
Raymond EversDepartment of Pharmaceutics, University of Washington, Seattle, Washington (L.W., C.C., E.J.K., J.D.U.); Pharmacokinetics, Pharmacodynamics, and Drug Metabolism, Merck & Co., Rahway, New Jersey (X.C.); Departments of Clinical Pharmacology and Drug Metabolism and Pharmacokinetics, Gilead Sciences, Inc., Foster City, California (A.S.R., A.M.); Drug Metabolism and Pharmacokinetics, Genentech, South San Francisco, California (L.S., C.E.C.A.H.); Preclinical PK and In Vitro ADME, Biogen, Cambridge, Massachusetts (G.X.); Pharmacokinetics, Pharmacodynamics, and Drug Metabolism, Ardea Biosciences, Inc., San Diego, California (C.L.); Pharmaceutical Candidate Optimization, Bristol-Myers Squibb Company, Princeton, New Jersey (Y.L.,W.H.); Takeda Pharmaceuticals International Co., Cambridge, Massachusetts (M.L.); Pharmacokinetics, Pharmacodynamics, and Drug Metabolism, Merck & Co., Kenilworth, New Jersey (R.E.); Department of Surgery, University of Kansas Medical Center, Kansas City, Kansas (S.C.K.).
William HumphreysDepartment of Pharmaceutics, University of Washington, Seattle, Washington (L.W., C.C., E.J.K., J.D.U.); Pharmacokinetics, Pharmacodynamics, and Drug Metabolism, Merck & Co., Rahway, New Jersey (X.C.); Departments of Clinical Pharmacology and Drug Metabolism and Pharmacokinetics, Gilead Sciences, Inc., Foster City, California (A.S.R., A.M.); Drug Metabolism and Pharmacokinetics, Genentech, South San Francisco, California (L.S., C.E.C.A.H.); Preclinical PK and In Vitro ADME, Biogen, Cambridge, Massachusetts (G.X.); Pharmacokinetics, Pharmacodynamics, and Drug Metabolism, Ardea Biosciences, Inc., San Diego, California (C.L.); Pharmaceutical Candidate Optimization, Bristol-Myers Squibb Company, Princeton, New Jersey (Y.L.,W.H.); Takeda Pharmaceuticals International Co., Cambridge, Massachusetts (M.L.); Pharmacokinetics, Pharmacodynamics, and Drug Metabolism, Merck & Co., Kenilworth, New Jersey (R.E.); Department of Surgery, University of Kansas Medical Center, Kansas City, Kansas (S.C.K.).
Cornelis E C A HopDepartment of Pharmaceutics, University of Washington, Seattle, Washington (L.W., C.C., E.J.K., J.D.U.); Pharmacokinetics, Pharmacodynamics, and Drug Metabolism, Merck & Co., Rahway, New Jersey (X.C.); Departments of Clinical Pharmacology and Drug Metabolism and Pharmacokinetics, Gilead Sciences, Inc., Foster City, California (A.S.R., A.M.); Drug Metabolism and Pharmacokinetics, Genentech, South San Francisco, California (L.S., C.E.C.A.H.); Preclinical PK and In Vitro ADME, Biogen, Cambridge, Massachusetts (G.X.); Pharmacokinetics, Pharmacodynamics, and Drug Metabolism, Ardea Biosciences, Inc., San Diego, California (C.L.); Pharmaceutical Candidate Optimization, Bristol-Myers Squibb Company, Princeton, New Jersey (Y.L.,W.H.); Takeda Pharmaceuticals International Co., Cambridge, Massachusetts (M.L.); Pharmacokinetics, Pharmacodynamics, and Drug Metabolism, Merck & Co., Kenilworth, New Jersey (R.E.); Department of Surgery, University of Kansas Medical Center, Kansas City, Kansas (S.C.K.).
Sean C KumerDepartment of Pharmaceutics, University of Washington, Seattle, Washington (L.W., C.C., E.J.K., J.D.U.); Pharmacokinetics, Pharmacodynamics, and Drug Metabolism, Merck & Co., Rahway, New Jersey (X.C.); Departments of Clinical Pharmacology and Drug Metabolism and Pharmacokinetics, Gilead Sciences, Inc., Foster City, California (A.S.R., A.M.); Drug Metabolism and Pharmacokinetics, Genentech, South San Francisco, California (L.S., C.E.C.A.H.); Preclinical PK and In Vitro ADME, Biogen, Cambridge, Massachusetts (G.X.); Pharmacokinetics, Pharmacodynamics, and Drug Metabolism, Ardea Biosciences, Inc., San Diego, California (C.L.); Pharmaceutical Candidate Optimization, Bristol-Myers Squibb Company, Princeton, New Jersey (Y.L.,W.H.); Takeda Pharmaceuticals International Co., Cambridge, Massachusetts (M.L.); Pharmacokinetics, Pharmacodynamics, and Drug Metabolism, Merck & Co., Kenilworth, New Jersey (R.E.); Department of Surgery, University of Kansas Medical Center, Kansas City, Kansas (S.C.K.).
Jashvant D UnadkatDepartment of Pharmaceutics, University of Washington, Seattle, Washington (L.W., C.C., E.J.K., J.D.U.); Pharmacokinetics, Pharmacodynamics, and Drug Metabolism, Merck & Co., Rahway, New Jersey (X.C.); Departments of Clinical Pharmacology and Drug Metabolism and Pharmacokinetics, Gilead Sciences, Inc., Foster City, California (A.S.R., A.M.); Drug Metabolism and Pharmacokinetics, Genentech, South San Francisco, California (L.S., C.E.C.A.H.); Preclinical PK and In Vitro ADME, Biogen, Cambridge, Massachusetts (G.X.); Pharmacokinetics, Pharmacodynamics, and Drug Metabolism, Ardea Biosciences, Inc., San Diego, California (C.L.); Pharmaceutical Candidate Optimization, Bristol-Myers Squibb Company, Princeton, New Jersey (Y.L.,W.H.); Takeda Pharmaceuticals International Co., Cambridge, Massachusetts (M.L.); Pharmacokinetics, Pharmacodynamics, and Drug Metabolism, Merck & Co., Kenilworth, New Jersey (R.E.); Department of Surgery, University of Kansas Medical Center, Kansas City, Kansas (S.C.K.) jash@uw.edu.
University of Kansas Medical Center · USMerck & Co., Inc., Rahway, NJ, USA (United States) · USBiogen (United States) · USBristol-Myers Squibb (United States) · USPharmacoGenetics (China) · CNUniversity of Washington · US
Funding
NLM NIH HHS HHSN276201200017C
Abstract
Although data are available on the change of expression/activity of drug-metabolizing enzymes in liver cirrhosis patients, corresponding data on transporter protein expression are not available. Therefore, using quantitative targeted proteomics, we compared our previous data on noncirrhotic control livers (n = 36) with the protein expression of major hepatobiliary transporters, breast cancer resistance protein (BCRP), bile salt export pump (BSEP), multidrug and toxin extrusion protein 1 (MATE1), multidrug resistance-associated protein (MRP)2, MRP3, MRP4, sodium taurocholate-cotransporting polypeptide (NTCP), organic anion-transporting polypeptides (OATP)1B1, 1B3, 2B1, organic cation transporter 1 (OCT1), and P-glycoprotein (P-gp) in alcoholic (n = 27) and hepatitis C cirrhosis (n = 30) livers. Compared with control livers, the yield of membrane protein from alcoholic and hepatitis C cirrhosis livers was significantly reduced by 56 and 67%, respectively. The impact of liver cirrhosis on transporter protein expression was transporter-dependent. Generally, reduced protein expression (per gram of liver) was found in alcoholic cirrhosis livers versus control livers, with the exception that the expression of MRP3 was increased, whereas no change was observed for MATE1, MRP2, OATP2B1, and P-gp. In contrast, the impact of hepatitis C cirrhosis on protein expression of transporters (per gram of liver) was diverse, showing an increase (MATE1), decrease (BSEP, MRP2, NTCP, OATP1B3, OCT1, and P-gp), or no change (BCRP, MRP3, OATP1B1, and 2B1). The expression of hepatobiliary transporter protein differed in different diseases (alcoholic versus hepatitis C cirrhosis). Finally, incorporation of protein expression of OATP1B1 in alcoholic cirrhosis into the Simcyp physiologically based pharmacokinetics cirrhosis module improved prediction of the disposition of repaglinide in liver cirrhosis patients. These transporter expression data will be useful in the future to predict transporter-mediated drug disposition in liver cirrhosis patients.
Indexed as
EthanolFemaleHepatitis CHepatocytesHumansLiverLiver CirrhosisMaleMembrane ProteinsMembrane Transport ProteinsMiddle AgedMultidrug Resistance-Associated Protein 2ProteomeProteomicsABCC2 protein, humanEthanolMembrane ProteinsMembrane Transport ProteinsMultidrug Resistance-Associated Protein 2Proteome
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