Effects of Hemodialysis on Methadone Pharmacokinetics and QTc

• Published in: Clinical therapeutics 2015-07, Vol.37 (7), p.1594-1599
• Main Authors: Opdal, Mimi Stokke, MD, PhD, Arnesen, Margrete, Müller, Lill Dannevig, Hullstein, Ingunn, Sayed, Karim, Brørs, Odd, Kringen, Marianne, Sagedal, Solbjørg, Gjesdal, Knut, Krajci, Peter
• Format: Article
• Language: English
• Subjects: Acids; Aged; Calibration; Conflicts of interest; Electrocardiography; Electrolytes; Female; Hemodialysis; Hemodialysis Solutions - chemistry; Hospitals; Humans; Internal Medicine; Kidney diseases; Kidney Failure, Chronic - metabolism; Kidney Failure, Chronic - therapy; Long QT Syndrome - etiology; Male; Medical Education; methadone; Methadone - pharmacokinetics; methadone maintenance treatment; Opiate Substitution Treatment - methods; Particle size; Patients; pharmacokinetics; Pore size; Potassium; QTc; Renal Dialysis - adverse effects; Renal Dialysis - methods; renal failure; Tandem Mass Spectrometry - methods; Urine
• ISSN: 0149-2918; 1879-114X
• DOI: 10.1016/j.clinthera.2015.04.009

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.