Effects of Hemodialysis on Methadone Pharmacokinetics and QTc

Clin Ther. 2015 Jul 1;37(7):1594-9. doi: 10.1016/j.clinthera.2015.04.009. Epub 2015 May 8.

Abstract

Purpose: Effects of hemodialysis on pharmacokinetic properties and QTc were studied in 4 patients taking daily methadone dose of 100 mg (range, 60-120 mg).

Methods: Methadone in serum, dialysate, and urine were measured by LC-MS/MS. QTc was calculated with Bazett's formula.

Findings: The serum Cmin methadone level was 1124 nmol/L (range, 547-1581 nmol/L). Methadone dialysate clearance was 17.1 mL/min (range, 13.7-20.6 mL/min). Total loss in dialysate was 2.30% (range, 1,25-3,70%) of daily methadone intake. QTc increased from 391 msec (range, 369-406 msec) to 445 msec (range, 407-479 msec), independently of serum methadone level, which may be explained by normalization of serum electrolytes.

Implications: Methadone dose adjustment is not needed because of hemodialysis.

Keywords: QTc; hemodialysis; methadone; methadone maintenance treatment; pharmacokinetics; renal failure.

MeSH terms

  • Aged
  • Electrocardiography
  • Female
  • Hemodialysis Solutions / chemistry
  • Humans
  • Kidney Failure, Chronic / metabolism
  • Kidney Failure, Chronic / therapy
  • Long QT Syndrome / etiology
  • Male
  • Methadone / pharmacokinetics*
  • Opiate Substitution Treatment / methods*
  • Renal Dialysis / adverse effects
  • Renal Dialysis / methods*
  • Tandem Mass Spectrometry / methods

Substances

  • Hemodialysis Solutions
  • Methadone