Electronic Thesis and Dissertation Repository

Degree

Master of Science

Program

Physiology and Pharmacology

Supervisor

Dr. Brad Urquhart

2nd Supervisor

Dr. Matthew Weir

Joint Supervisor

Abstract

Of the minimal information describing drug dialyzability, the majority was obtained prior to modern hemodialysis membranes. This study characterized the dialyzability of the most commonly prescribed beta blockers in patients undergoing high-flux hemodialysis. Eight subjects were recruited to a pharmacokinetic, 4-way crossover trial. Drug concentrations were measured using mass spectrometry and dialyzability determined by the arterial-venous difference and recovery clearance methods. A provincial-wide retrospective cohort study was designed to determine the effect of dialyzability on adverse clinical outcomes. Beta blocker efficacy can be hindered if substantial clearance occurs during dialysis. Our results demonstrate atenolol and metoprolol are extensively cleared during hemodialysis, while carvedilol displays low dialyzability. Although bisoprolol was previously considered to be minimally dialyzed, we now demonstrate moderate dialyzability. This highlights the importance of conducting dialyzability studies. With recent findings suggesting heightened mortality risk in hemodialysis patients prescribed highly dialyzed beta blockers, dialyzability data is critical to optimize pharmacotherapy.

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