Electronic Thesis and Dissertation Repository

Degree

Master of Science

Program

Physiology and Pharmacology

Supervisor(s)

Dr. Brad Urquhart

Abstract

Chronic kidney disease (CKD) is characterized by a progressive and irreversible decline in renal function. Patients are at high risk for adverse drug events since they are typically administered multiple medications concurrently and pharmacokinetic changes in the diseased state are relatively unexplored. Recent studies point towards molecules known as uremic toxins for playing a mechanistic role in altering the expression and function of drug metabolizing enzymes and drug transporter proteins. To further investigate this hypothesis an adenine-induced model of CKD was used in male wistar rats. AST-120 was administered to remove uremic toxins in an attempt to recover metabolic enzyme as well as transporter protein function and activity. Animals were injected with rosuvastatin prior to sacrifice as a probe for transporter function. Impaired organic anion transporting polypeptide (OATP) and cytochrome P450 (CYP) function are important to acknowledge in a clinical setting since both of these protein superfamilies have broad substrate specificities. We have shown significant down regulation in CYP2B1 activity and expression in rats (P


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