Abstracts

Rationale: Plasma exchange (PEX) is an effective treatment for various immune mediated neurological conditions (1) and consists of exchanging the plasma with 5% albumin. During the process the content of plasma is discarded, which includes solutes and protein bound molecules. Understanding the effect of PEX on anti-epileptic drug concentrations is required for appropriate management of epilepsy patients undergoing PEX. Although there is strong evidence that the levels of the antiepileptic drug levetiracetam (LEV) drop by about 50% after 4 hours of hemodialysis thereby requiring additional dose after each session (8), there are no reports of the effect of PEX on the level of LEV in the literature. We present a case of a woman with epilepsy and neuromyelitis optica requiring PEX while taking levetiracetam.Methods: A 52-year-old woman with a history of seropositive NMO and non-convulsive status epilepticus well controlled on LEV 500 mg twice a day, presented with increased weakness in her legs due to NMO exacerbation. She was started on PEX and received a total of 4 sessions. LEV levels were obtained using Liquid Chromatography and Tandem Mass Spectrometry before and after each PEX to provide recommendations for adequate dosing scheduling. During each PEX session, 3.7 L of plasma were exchanged with 5% albumin over two hours. Statistical analysis was performed using Wilcoxen singed-rank test, given the small number of samples. We assumed a volume of distribution (Vd) of 0.5 and half-life of 8 hours to perform basic pharmacokinetic estimation of the expected change in LEV levels after such a 2-hour session.Results: Patient tolerated all the sessions, without any breakthrough seizures during the admission. She continued her twice daily dose of LEV 500 mg, and was given an extra dose of LEV 1000 mg after the second session and 500 mg after the third session (both after blood levels were drawn.) The average pre-exchange and post-exchange LEV levels were 23.4 and 19.2, respectively (17.9% absolute reduction, one-tail Wilcoxen singed-rank test p-value 0.054). We expected a decrease of about 16% due to elimination given a half-life of 8 hours. The expected maximum decrease after removal of 3.7 L of plasma, given the Vd of 0.5 L/kg (or 40 L for our patient) would be about 10%, bringing the expected upper limit of reduction after 2 hours of PLEX to about 26% based on simple pharmacokinetics.Conclusions: Levetiracetam has no significant protein binding with a volume of distribution of 0.5-0.7 L/Kg and it is excreted unchanged in the urine (9). Although we observed a consistent decreasing trend in LEV plasma levels following PEX, the absolute reduction in the LEV plasma concentrations were in the range that is expected from elimination of drug alone. Therefore, our current results do not support a role for LEV supplemental dose after PEX. We are in the process of collecting more data to achieve a higher statistical power, and better modeling of pharmacokinetics of LEV after PEX.