Sodium Valproate Dialysability in Patients with Impaired Renal Function
Sodium valproate is partially dialysable in patients with impaired renal function, with hemodialysis typically reducing valproate concentrations by approximately 20%. 1
Pharmacokinetic Properties Affecting Dialysability
- Valproate is primarily eliminated via hepatic metabolism (80%) with only 20% renal clearance, making it less dependent on kidney function for elimination 1
- At therapeutic concentrations, valproate is highly protein-bound (90-95%), which normally limits its dialysability 2
- In patients with renal failure, protein binding of valproate is substantially reduced, increasing the free fraction available for dialysis 1, 3
- The half-life of valproate ranges from 9-16 hours in adults with normal renal function 1
Dialysability in Renal Impairment
- Hemodialysis typically reduces valproate concentrations by about 20%, which is clinically significant enough to consider in dosing but does not require major dose adjustments 1
- In patients with renal failure (creatinine clearance <10 mL/minute), there is a slight reduction (27%) in the unbound clearance of valproate 1
- Protein binding is substantially reduced in patients with renal failure, making more free drug available for dialysis removal 1, 3
- In overdose situations, protein binding becomes saturated, resulting in higher free valproate concentrations that are more effectively removed by dialysis 2, 4
Clinical Implications
- No dosage adjustment is generally necessary for patients with renal failure on regular valproate therapy 1
- Monitoring total valproate concentrations may be misleading in patients with renal impairment due to altered protein binding; free valproate concentrations provide a more accurate assessment 1, 5
- Post-dialysis rebound of valproate levels can occur as the drug redistributes from tissue stores, which may require consideration in dosing strategies 4
- Hemodialysis may be an effective treatment option in cases of severe valproate overdose, particularly when protein binding is saturated 2
Special Considerations
- The dialysability of valproate differs from other antiepileptic drugs - some are highly dialysable (e.g., gabapentin, levetiracetam) while others have limited dialysability similar to valproate 6
- Free fatty acid concentrations, which increase during dialysis, can further affect valproate protein binding and free drug concentrations 5
- Different dialysis modalities may have varying effects on valproate removal - standard hemodialysis, hemoperfusion, and sustained low-efficiency dialysis with filtration (SLEDD-f) have all been used in overdose situations 2, 4
Monitoring Recommendations
- Monitor for clinical efficacy and adverse effects in patients on valproate who undergo regular dialysis 1
- Consider measuring free valproate concentrations rather than total concentrations in patients with renal impairment 1, 5
- Be aware that the therapeutic range (commonly 50-100 μg/mL of total valproate) may not apply directly to patients with renal impairment due to altered protein binding 1