Kim L. R. Brouwer
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View article: Comparison of Metformin <scp>PBPK</scp> Models Incorporating Placental Transfer to Predict Fetal and Maternal Exposure
Comparison of Metformin <span>PBPK</span> Models Incorporating Placental Transfer to Predict Fetal and Maternal Exposure Open
Physiologically based pharmacokinetic (PBPK) modeling of placental drug transfer is an evolving tool for predicting fetal drug exposure. In this study, a pregnancy‐specific metformin PBPK model was developed, and the following four approac…
View article: Impact of Obesity and <scp>MASH</scp> on Zonal Hepatocellular Statin Exposure: Pharmacodynamic Insights From a Permeability‐Limited Multicompartment Liver Model
Impact of Obesity and <span>MASH</span> on Zonal Hepatocellular Statin Exposure: Pharmacodynamic Insights From a Permeability‐Limited Multicompartment Liver Model Open
Statins are frequently prescribed for hyperlipidemia, a common comorbidity in patients with obesity and/or metabolic dysfunction‐associated steatohepatitis (MASH). However, limited knowledge exists on how MASH may alter statin disposition …
View article: Species-Dependent Metabolism of a Covalent nsP2 Protease Inhibitor with In Vivo Antialphaviral Activity
Species-Dependent Metabolism of a Covalent nsP2 Protease Inhibitor with In Vivo Antialphaviral Activity Open
RA-0002034 (1) is a potent covalent inhibitor targeting the nsP2 cysteine protease. The species-dependent pharmacokinetics and metabolism of 1 were investigated to evaluate its therapeutic potential. Pharm…
View article: Species-Dependent Metabolism of a Covalent nsP2 Protease Inhibitor with In Vivo Antialphaviral Activity
Species-Dependent Metabolism of a Covalent nsP2 Protease Inhibitor with In Vivo Antialphaviral Activity Open
RA-0002034 (1) is a potent covalent inhibitor targeting the nsP2 cysteine protease. The species-dependent pharmacokinetics and metabolism of 1 were investigated to evaluate its therapeutic potential. Pharmacokinetic profiling…
View article: Species Dependent Metabolism of a Covalent nsP2 Protease Inhibitor with <i>in Vivo</i> Anti-alphaviral Activity
Species Dependent Metabolism of a Covalent nsP2 Protease Inhibitor with <i>in Vivo</i> Anti-alphaviral Activity Open
RA-0002034 ( 1 ) is a potent covalent inhibitor targeting the alphavirus nsP2 cysteine protease. The species-dependent pharmacokinetics and metabolism of 1 were investigated to evaluate its therapeutic potential. Pharmacokinetic profiling …
View article: Hepatic OATP1B zonal distribution: Implications for rifampicin‐mediated drug–drug interactions explored within a PBPK framework
Hepatic OATP1B zonal distribution: Implications for rifampicin‐mediated drug–drug interactions explored within a PBPK framework Open
OATP1B facilitates the uptake of xenobiotics into hepatocytes and is a prominent target for drug-drug interactions (DDIs). Reduced systemic exposure of OATP1B substrates has been reported following multiple-dose rifampicin; one explanation…
View article: Effects of PFAS on human liver transporters: implications for health outcomes
Effects of PFAS on human liver transporters: implications for health outcomes Open
Per- and polyfluoroalkyl substances (PFAS) have become internationally recognized over the past three decades as persistent organic pollutants used in the production of various consumer and industrial goods. Research efforts continue to ga…
View article: Prediction of Altered Bile Acid Disposition Due to Inhibition of Multiple Transporters: An Integrated Approach Using Sandwich-Cultured Hepatocytes, Mechanistic Modeling, and Simulation
Prediction of Altered Bile Acid Disposition Due to Inhibition of Multiple Transporters: An Integrated Approach Using Sandwich-Cultured Hepatocytes, Mechanistic Modeling, and Simulation Open
Transporter-mediated alterations in bile acid disposition may have significant toxicological implications. Current methods to predict interactions are limited by the interplay of multiple transporters, absence of protein in the experimenta…
View article: Nanoparticle Drug Delivery Can Reduce the Hepatotoxicity of Therapeutic Cargo
Nanoparticle Drug Delivery Can Reduce the Hepatotoxicity of Therapeutic Cargo Open
Hepatotoxicity is a key concern in the clinical translation of nanotherapeutics because preclinical studies have consistently shown that nanotherapeutics accumulates extensively in the liver. However, clinical-stage nanotherapeutics have n…
View article: Hepatic OATP1B zonal distribution: Implications for rifampicin‐mediated drug–drug interactions explored within a PBPK framework
Hepatic OATP1B zonal distribution: Implications for rifampicin‐mediated drug–drug interactions explored within a PBPK framework Open
OATP1B facilitates the uptake of xenobiotics into hepatocytes and is a prominent target for drug–drug interactions (DDIs). Reduced systemic exposure of OATP1B substrates has been reported following multiple‐dose rifampicin; one explanation…
View article: Effects of PFAS on human liver transporters: implications for health outcomes
Effects of PFAS on human liver transporters: implications for health outcomes Open
Per- and polyfluoroalkyl substances (PFAS) have become internationally recognized over the past three decades as persistent organic pollutants used in the production of various consumer and industrial goods. Research efforts continue to ga…
View article: Issue Information
Issue Information Open
Clinical and Translational Science highlights original research that helps bridge laboratory discovery with the diagnosis and treatment of human disease.Research may appear as Articles, Commentaries, Point-Counterpoint, Phase Forwards, Rev…
View article: Alterations in zonal distribution and plasma membrane localization of hepatocyte bile acid transporters in patients with NAFLD
Alterations in zonal distribution and plasma membrane localization of hepatocyte bile acid transporters in patients with NAFLD Open
Background: NAFLD is highly prevalent with limited treatment options. Bile acids (BAs) increase in the systemic circulation and liver during NAFLD progression. Changes in plasma membrane localization and zonal distribution of BA transporte…
View article: Membrane transporters in drug development and as determinants of precision medicine
Membrane transporters in drug development and as determinants of precision medicine Open
View article: Issue Information
Issue Information Open
Clinical and Translational Science highlights original research that helps bridge laboratory discovery with the diagnosis and treatment of human disease.Research may appear as Articles, Commentaries, Point-Counterpoint, Phase Forwards, Rev…
View article: Issue Information
Issue Information Open
Clinical and Translational Science highlights original research that helps bridge laboratory discovery with the diagnosis and treatment of human disease. Research may appear as Articles
View article: Hepatic Bile Acid Transporters and Drug-induced Hepatotoxicity
Hepatic Bile Acid Transporters and Drug-induced Hepatotoxicity Open
Drug-induced liver injury (DILI) remains a major concern in drug development from a patient safety perspective because it is the leading cause of acute liver failure. One mechanism of DILI is altered bile acid homeostasis and involves seve…
View article: Application of Pharmacokinetic Modeling to Characterize Hepatobiliary Disposition of Imaging Agents and Alterations due to Liver Injury in Isolated Perfused Rat Livers
Application of Pharmacokinetic Modeling to Characterize Hepatobiliary Disposition of Imaging Agents and Alterations due to Liver Injury in Isolated Perfused Rat Livers Open
View article: Effect of mTOR inhibitors on sodium taurocholate cotransporting polypeptide (NTCP) function in vitro
Effect of mTOR inhibitors on sodium taurocholate cotransporting polypeptide (NTCP) function in vitro Open
The sodium taurocholate cotransporting polypeptide (NTCP; gene name SLC10A1 ) is the primary hepatic basolateral uptake transporter for conjugated bile acids and the entry receptor for the hepatitis B and D virus (HBV/HDV). Regulation of h…
View article: Developing evidence-based resources for evaluating postgraduate trainees in the biomedical sciences
Developing evidence-based resources for evaluating postgraduate trainees in the biomedical sciences Open
Postgraduate trainees elevate the academic strength of institutions by conducting research, promoting innovation, securing grant funding, training undergraduate students, and building alliances. Rigorous and systematic program evaluation c…
View article: A novel differentiated HuH-7 cell model to examine bile acid metabolism, transport and cholestatic hepatotoxicity
A novel differentiated HuH-7 cell model to examine bile acid metabolism, transport and cholestatic hepatotoxicity Open
View article: Clinical Relevance of Hepatic and Renal P‐gp/<scp>BCRP</scp> Inhibition of Drugs: An International Transporter Consortium Perspective
Clinical Relevance of Hepatic and Renal P‐gp/<span>BCRP</span> Inhibition of Drugs: An International Transporter Consortium Perspective Open
The role of P‐glycoprotein (P‐gp) and breast cancer resistance protein (BCRP) in drug–drug interactions (DDIs) and limiting drug absorption as well as restricting the brain penetration of drugs with certain physicochemical properties is we…
View article: Considerations for Physiologically Based Modeling in Liver Disease: From Nonalcoholic Fatty Liver (NAFL) to Nonalcoholic Steatohepatitis (NASH)
Considerations for Physiologically Based Modeling in Liver Disease: From Nonalcoholic Fatty Liver (NAFL) to Nonalcoholic Steatohepatitis (NASH) Open
Nonalcoholic fatty liver disease (NAFLD), representing a clinical spectrum ranging from nonalcoholic fatty liver (NAFL) to nonalcoholic steatohepatitis (NASH), is rapidly evolving into a global pandemic. Patients with NAFLD are burdened wi…
View article: Regulation of Drug Transport Proteins—From Mechanisms to Clinical Impact: A White Paper on Behalf of the International Transporter Consortium
Regulation of Drug Transport Proteins—From Mechanisms to Clinical Impact: A White Paper on Behalf of the International Transporter Consortium Open
Membrane transport proteins are involved in the absorption, disposition, efficacy, and/or toxicity of many drugs. Numerous mechanisms (e.g., nuclear receptors, epigenetic gene regulation, microRNAs, alternative splicing, post‐translational…
View article: Lipidomics profiles in hepatocytes from nonalcoholic steatohepatitis patients differ markedly from <i>in vitro</i>‐induced steatotic hepatocytes
Lipidomics profiles in hepatocytes from nonalcoholic steatohepatitis patients differ markedly from <i>in vitro</i>‐induced steatotic hepatocytes Open
Nonalcoholic steatohepatitis (NASH) is a severe form of liver injury that can be caused by a variety of stimuli and has a significant mortality rate. A common technique to induce in vitro steatosis involves culturing primary human hepatocy…
View article: Novel Bile Acid-Dependent Mechanisms of Hepatotoxicity Associated with Tyrosine Kinase Inhibitors
Novel Bile Acid-Dependent Mechanisms of Hepatotoxicity Associated with Tyrosine Kinase Inhibitors Open
View article: New Pharmacokinetic Parameters of Imaging Substrates Quantified from Rat Liver Compartments
New Pharmacokinetic Parameters of Imaging Substrates Quantified from Rat Liver Compartments Open
View article: Identification of Key Amino Acids that Impact Organic Solute Transporter α/β (OSTα/β)
Identification of Key Amino Acids that Impact Organic Solute Transporter α/β (OSTα/β) Open
View article: Moving Towards FAIR Data Practices in Pharmacy Education
Moving Towards FAIR Data Practices in Pharmacy Education Open
Pharmacy schools are generating significant amounts of data across the training continuum, including data about student selection, performance, and job placement. However, current data practices limit the Academy's ability to effectively l…
View article: Identification of Hepatic Phospholipidosis Inducers in Sandwich-Cultured Rat Hepatocytes, a Physiologically Relevant Model, Reveals Altered Basolateral Uptake and Biliary Excretion of Anionic Probe Substrates
Identification of Hepatic Phospholipidosis Inducers in Sandwich-Cultured Rat Hepatocytes, a Physiologically Relevant Model, Reveals Altered Basolateral Uptake and Biliary Excretion of Anionic Probe Substrates Open
Drug-induced phospholipidosis (PLD) is characterized by phospholipid accumulation within the lysosomes of affected tissues, resulting in lysosomal enlargement and laminar body inclusions. Numerous adverse effects and toxicities have been l…