Antiepileptic drugs (AEDs) are cleared from the circulation by hemodialysis, principally by diffusion from the blood into the dialysate through the filter membrane. The drug moves from the blood (high concentration) to the dialysate (low concentration) via a concentration gradient. (The principles applicable to hemodialysis also apply to peritoneal dialysis.)

Many factors determine the rate of clearance of a drug during hemodialysis:29

• Water solubility. Water-soluble drugs readily cross dialysis membranes, whereas drugs that are not readily water-soluble do not. Many CNS drugs (e.g., carbamazepine, phenytoin, tricyclic antidepressants) are lipid-soluble compounds that are not readily water-soluble. (Lipid solubility permits passage across the blood-brain barrier.)



• Protein binding. Only non–protein-bound drugs can cross dialysis membranes. Drugs that are highly protein-bound (e.g., phenytoin, valproate) are difficult to remove from the systemic circulation by hemodialysis.



• Volume of distribution. Drugs that remain mainly in the blood are more readily removed than drugs that are distributed extensively into tissues.



• Molecular size. Drugs must pass through pores of a specified size during hemodialysis. Molecules larger than 500 atomic mass units usually do not pass through hemodialysis filters. AEDs have atomic masses less than 500, however, so molecular size is not an issue for dialysis of AEDs.



• Dialysis conditions. There are many types of dialysis filters. Filter characteristics, filter size, blood flow rate, and dialysis flow rate all affect the hemodialysis clearance of a drug.

There is no simple equation to predict the amount of an AED that will be lost during dialysis. Drugs that are water-soluble, not highly protein-bound, and that have a small volume of distribution are readily removed by hemodialysis. Drugs with high lipid solubility (i.e., low water solubility), high protein binding, and high volume of distribution will be difficult to remove by hemodialysis.

See Table: Risk of Drug Removal By Hemodialysis for a listing of risk of drug removal by hemodialysis for various AEDs. Note that some removal occurs during dialysis even for “low-risk" drugs.

Adapted from: Browne TR. Renal disorders. In: Ettinger AB and Devinsky O, eds. Managing epilepsy and co-existing disorders. Boston: Butterworth-Heinemann; 2002;49-62. With permission from Elsevier (www.elsevier.com).

Reviewed and revised February 2004 by Steven C. Schachter, MD, epilepsy.com Editorial Board.