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Full-Text Articles in Life Sciences
Non-Renal Alterations Of Drug Disposition In Chronic Kidney Disease, Nicholas Tonial
Non-Renal Alterations Of Drug Disposition In Chronic Kidney Disease, Nicholas Tonial
Electronic Thesis and Dissertation Repository
Chronic kidney disease (CKD) results in profound changes to non-renal drug elimination pathways including hepatic drug metabolism and hepatic transport mediated excretion. This results in complex pharmacological changes to drug disposition in the setting of kidney dysfunction. Four million Canadians are affected by CKD and the average CKD patient takes 14 medications daily with up to 40% experiencing adverse drug reactions at some point in their disease progression. Better elucidation of these changes in the setting of CKD is required to properly dose medications to provide therapeutic benefits while minimizing toxicity. This thesis aimed to better understand the impact kidney …
Expression Of Hepatic Cytochrome P450 Drug Metabolizing Enzymes In Diabetes And Diabetic Nephropathy, Cheng Jay Fang
Expression Of Hepatic Cytochrome P450 Drug Metabolizing Enzymes In Diabetes And Diabetic Nephropathy, Cheng Jay Fang
Electronic Thesis and Dissertation Repository
The prevalence of diabetes worldwide is rapidly increasing. Polypharmacy, along with a high risk of adverse drug reactions, is common in diabetic patients. Cytochrome P450 (CYP) 3A and 2C drug metabolizing enzymes are reduced in chronic kidney disease (CKD), altering drug pharmacokinetics and contributing to adverse drug reactions. A large fraction of commonly prescribed drugs are metabolized by CYP3A and CYP2C. Approximately 40% of all CKD cases are attributed to diabetic nephropathy (DN) and early DN presents as mild kidney disease. This study aims to evaluate the impact of diabetes and DN on levels and activity of hepatic CYP3A and …
Regulation Of Hepatic Drug Metabolizing Enzymes In Chronic Kidney Disease, Thomas J. Velenosi
Regulation Of Hepatic Drug Metabolizing Enzymes In Chronic Kidney Disease, Thomas J. Velenosi
Electronic Thesis and Dissertation Repository
Chronic kidney disease (CKD) occurs as a result of declining renal function for 3 or more months. CKD effects 1 in 10 Canadians and is associated with a number of co-morbidities including diabetes and cardiovascular disease. To manage CKD and associated co-morbidities, patients take an average of 12 medications with a median pill burden of 19. Indeed, renal drug elimination is compromised in CKD, as declining glomerular filtration reduces drug excretion into urine. More recently, studies have provided evidence of altered non-renal drug clearance in CKD. The majority of drug clearance occurs in the liver by CYP2C and CYP3A drug …
Cytochrome P450 3a4 Expression And Regulation In Non-Alcoholic Fatty Liver Disease, Sarah J. Woolsey
Cytochrome P450 3a4 Expression And Regulation In Non-Alcoholic Fatty Liver Disease, Sarah J. Woolsey
Electronic Thesis and Dissertation Repository
Non-alcoholic fatty liver disease (NAFLD) is defined as lipid accumulation within hepatocytes (steatosis) in the absence of excess alcohol consumption. It is the most common liver disease in the western world, affecting one third of the general adult population with particularly high prevalence in obesity and type 2 diabetes. NAFLD is a disease continuum originating with simple hepatic steatosis that can progress to non-alcoholic steatohepatitis (NASH) with fibrosis and potentially cirrhosis, which places patients at risk for hepatocellular carcinoma. Unfortunately, there are not yet specific pharmacologic agents to treat NAFLD and so its management involves treatment of comorbidities, but there …
Erythropoietin And Chronic Kidney Disease Alter Hepatic Expression Of Cytochrome P450 Enzymes And Drug Transport Proteins, David A. Feere
Erythropoietin And Chronic Kidney Disease Alter Hepatic Expression Of Cytochrome P450 Enzymes And Drug Transport Proteins, David A. Feere
Electronic Thesis and Dissertation Repository
Chronic kidney disease (CKD) is a progressive disease involving the irreversible loss of kidney function. Patients with CKD require concurrent dosing of many medications to manage their disease and associated comorbidities. Pharmacokinetic studies using patients with CKD and previous studies using animal models of CKD have demonstrated changes in hepatic drug metabolism and transport. Our studies aim to examine the effects that end-stage renal disease (ESRD) and continuous dosing of recombinant human erythropoietin (EPO) have on hepatic cytochrome P450 (P450) drug metabolizing enzymes and drug transport proteins. We used an adenine-fed rat model of CKD to demonstrate that EPO decreases …