Leflunomide in dialysis patients with rheumatoid arthritis--a pharmacokinetic study

Clin Rheumatol. 2013 Feb;32(2):267-70. doi: 10.1007/s10067-012-2122-1. Epub 2012 Nov 22.

Abstract

Pharmacokinetic data of disease modifying antirheumatic drugs during hemodialysis are limited to sulfasalazine, methotrexate, and cyclosporine. Only respective anecdotal data have been reported on leflunomide. We repeatedly measured teriflunomide (A77-1726), the active metabolite of leflunomide, during standard hemodialysis sessions and calculated teriflunomide clearances in five patients with rheumatoid arthritis (RA) and end-stage renal disease. The calculated teriflunomide clearances during a standardized dialysis session of 3-4.5 h at a blood flow rate of 160-300 ml/min were between 0 and 4.3 ml/min, the mean clearances of the total dialysis ranged between 1.1 and 3.4 ml/min. Total amount of teriflunomide removed was 5.8-8.8 μg per dialysis session. Dialytic removal of the active metabolite of leflunomide, teriflunomide (A77-1726), is negligible. Leflunomide can be used for RA patients on chronic dialysis without any dosage modification.

MeSH terms

  • Adult
  • Aged
  • Aged, 80 and over
  • Antirheumatic Agents / blood
  • Antirheumatic Agents / chemistry
  • Antirheumatic Agents / pharmacokinetics*
  • Arthritis, Rheumatoid / complications
  • Arthritis, Rheumatoid / drug therapy*
  • Crotonates / blood
  • Crotonates / chemistry
  • Female
  • Humans
  • Hydroxybutyrates
  • Isoxazoles / blood
  • Isoxazoles / chemistry
  • Isoxazoles / pharmacokinetics*
  • Kidney Failure, Chronic / complications
  • Kidney Failure, Chronic / therapy*
  • Leflunomide
  • Male
  • Middle Aged
  • Models, Biological
  • Nitriles
  • Renal Dialysis*
  • Retrospective Studies
  • Toluidines / blood
  • Toluidines / chemistry

Substances

  • Antirheumatic Agents
  • Crotonates
  • Hydroxybutyrates
  • Isoxazoles
  • Nitriles
  • Toluidines
  • teriflunomide
  • Leflunomide