Metoprolol (Toprol) Dialyzability
Metoprolol is only slightly dialyzable and should not be relied upon for removal by hemodialysis in most clinical situations. 1
Dialyzability Classification
The EXTRIP workgroup systematically reviewed beta-blockers and classified metoprolol as "slightly dialyzable" by intermittent hemodialysis, placing it in a middle category between extensively dialyzable drugs (like atenolol) and non-dialyzable drugs (like propranolol or carvedilol). 1
Clinical Evidence of Dialytic Clearance
Recent pharmacokinetic studies using modern high-flux hemodialysis membranes demonstrate measurable but limited removal:
- Recovery clearance method: 87 ml/min dialytic clearance 2
- Arterial-venous difference method: 114 ml/min dialytic clearance 2
- These clearance values are substantially lower than atenolol (167 ml/min) but higher than carvedilol (essentially 0%) 2
Pharmacokinetic Properties Affecting Dialyzability
Metoprolol's limited dialyzability is explained by its pharmacokinetic characteristics:
- Primary elimination: Hepatic metabolism via CYP2D6, not renal excretion 3, 4
- Renal excretion of unchanged drug: Less than 10% in extensive metabolizers (up to 30-40% in poor CYP2D6 metabolizers) 3
- Oral bioavailability: Approximately 50% due to first-pass metabolism 3
- Elimination half-life: 3-4 hours in normal metabolizers (7-9 hours in poor metabolizers) 3
Clinical Implications for Dialysis Patients
Dosing Considerations
- No routine dose adjustment required for patients with renal impairment on hemodialysis, as elimination is primarily hepatic 3
- The systemic availability and half-life do not differ clinically significantly between patients with renal failure and those with normal renal function 3
Poisoning/Overdose Context
- Hemodialysis is not recommended as a primary treatment for metoprolol poisoning due to its slight dialyzability 1
- The EXTRIP workgroup did not develop specific recommendations for metoprolol in poisoning cases due to insufficient clinical data, despite its classification as slightly dialyzable 1
Metabolite Considerations
- Active metabolites of metoprolol may be partially removed by dialysis, which could explain improved glucose response to glucagon after dialysis in some studies 5
- This metabolite removal may have clinical relevance for glucose metabolism in dialysis patients 5
Key Clinical Pitfall
Do not assume metoprolol requires supplemental dosing after hemodialysis. Unlike atenolol (which is extensively dialyzable and requires post-dialysis supplementation), metoprolol's hepatic metabolism means dialysis has minimal impact on total drug clearance. 3, 2