Key result
Atenolol, metoprolol, and bisoprolol undergo extensive hemodialysis clearance compared to negligible removal of carvedilol.
Why the study?
Does high-flux hemodialysis clear atenolol, metoprolol, bisoprolol, and carvedilol in patients on maintenance hemodialysis?
RCT (n=8)
Open-label
random order
Does high-flux hemodialysis clear atenolol, metoprolol, bisoprolol, and carvedilol in patients on maintenance hemodialysis?
Atenolol, metoprolol, and bisoprolol are significantly cleared by high-flux hemodialysis, whereas carvedilol has negligible clearance, which may impact drug selection and dosing in dialysis patients.
Answers are grounded in this paper and cite their sources.
May inform beta-blocker selection favoring carvedilol in hemodialysis; extends RCT pharmacokinetic data to high-flux dialysis.
Background and objectives There is a paucity of data available to describe drug dialyzability. Of the available information, most was obtained before implementation of modern hemodialysis membranes. Our study characterized dialyzability of the most commonly prescribed β -blockers in patients undergoing high-flux hemodialysis. Design, setting, participants, & measurements Patients on hemodialysis ( n =8) were recruited to an open label, pharmacokinetic, four-way crossover trial. Single doses of atenolol, metoprolol, bisoprolol, and carvedilol were administered on separate days in random order to each patient. Plasma and dialysate drug concentrations were measured, and dialyzability was determined by the recovery clearance and arterial venous difference methods. Results Using the recovery clearance method, the dialytic clearance values for atenolol, metoprolol, bisoprolol, and carvedilol were 72, 87, 44, and 0.2 ml/min, respectively ( P <0.001). Applying the arterial venous difference method, the dialytic clearance values of atenolol, metoprolol, bisoprolol, and carvedilol were 167, 114, 96, and 24 ml/min, respectively ( P <0.001). Conclusions Atenolol and metoprolol are extensively cleared by hemodialysis compared with the negligible dialytic clearance of carvedilol. Contrary to estimates of dialyzability on the basis of previous literature, our data indicate that bisoprolol is also dialyzable. This finding highlights the importance of conducting dialyzability studies to definitively characterize drug dialytic clearance.
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Tieu et al. (2018) conducted an RCT in maintenance hemodialysis (n=8). atenolol, metoprolol, bisoprolol, and carvedilol was evaluated on dialytic clearance (p=<0.001). Atenolol, metoprolol, and bisoprolol are extensively cleared by hemodialysis (recovery clearance 72, 87, and 44 ml/min) compared with negligible clearance of carvedilol (0.2 ml/min; P<0.001).
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