Eur J Clin Pharmacol DOI 10.1007/s00228-013-1628-z
LETTER TO THE EDITORS
Hemodialysis effects on phenytoin pharmacokinetics Sarah Bezzaoucha & Amine Merghoub & Caroline Lamarche & Vincent Pichette & Jean-Philippe Lafrance & Louis-Philippe Laurin & Michel Vallée & Robert Robitaille & Martine Leblanc & Robert Bell
Received: 24 October 2013 / Accepted: 8 December 2013 # Springer-Verlag Berlin Heidelberg 2014
Dear editor, Seizure disorders in patients with end-stage renal disease (ESRD) are frequent, and it is not uncommon for patients undergoing maintenance hemodialysis to receive phenytoin as anticonvulsant therapy. The plasma protein binding of phenytoin in these patients is usually reported to be reduced, mainly due to the accumulation of uremic compounds in the serum, which displace phenytoin from protein binding sites [1]. This decreased binding commonly requires frequent monitoring and dosing adjustment in response to the increase in the pharmacologically active, free fraction of phenytoin [1]. Because of the significant variability in the free fraction of phenytoin among patients with ESRD and the increased volume of distribution of the bound drug, dosage adjustment is usually based on free, rather than total phenytoin levels for anticonvulsant efficacy [2]. Accordingly, the accepted concentration range for total phenytoin should be reduced by 50 % in ESRD patients (20–40 μmol/L) in comparison to normal therapeutic range for phenytoin (40–80 μmol/L) to produce a suitable anticonvulsant effect with free phenytoin levels within the reference range (4–8 μmol/L) [3]. Whether hemodialysis may affect phenytoin plasma concentrations by partial removal of uremic compounds (and, therefore, protein S. Bezzaoucha : A. Merghoub : C. Lamarche : V. Pichette : J.
LETTER TO THE EDITORS
Hemodialysis effects on phenytoin pharmacokinetics Sarah Bezzaoucha & Amine Merghoub & Caroline Lamarche & Vincent Pichette & Jean-Philippe Lafrance & Louis-Philippe Laurin & Michel Vallée & Robert Robitaille & Martine Leblanc & Robert Bell
Received: 24 October 2013 / Accepted: 8 December 2013 # Springer-Verlag Berlin Heidelberg 2014
Dear editor, Seizure disorders in patients with end-stage renal disease (ESRD) are frequent, and it is not uncommon for patients undergoing maintenance hemodialysis to receive phenytoin as anticonvulsant therapy. The plasma protein binding of phenytoin in these patients is usually reported to be reduced, mainly due to the accumulation of uremic compounds in the serum, which displace phenytoin from protein binding sites [1]. This decreased binding commonly requires frequent monitoring and dosing adjustment in response to the increase in the pharmacologically active, free fraction of phenytoin [1]. Because of the significant variability in the free fraction of phenytoin among patients with ESRD and the increased volume of distribution of the bound drug, dosage adjustment is usually based on free, rather than total phenytoin levels for anticonvulsant efficacy [2]. Accordingly, the accepted concentration range for total phenytoin should be reduced by 50 % in ESRD patients (20–40 μmol/L) in comparison to normal therapeutic range for phenytoin (40–80 μmol/L) to produce a suitable anticonvulsant effect with free phenytoin levels within the reference range (4–8 μmol/L) [3]. Whether hemodialysis may affect phenytoin plasma concentrations by partial removal of uremic compounds (and, therefore, protein S. Bezzaoucha : A. Merghoub : C. Lamarche : V. Pichette : J.
