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• W2011051663 abstract "Methadone is known to be associated with prolongation of corrected QT time (QTc). Excretion of methadone is primarily renal in patients with normal renal function. It is unknown to what extent hemodialysis removes methadone. We investigated methadone kinetics and QTc during hemodialysis in methadone maintenance treatment (MMT) patients with end-stage renal disease. The Regional Ethics Committee approved the study. Data are given as median (range). Four patients with end-stage renal failure, 1 female and 3 males, 46 (43–53) years, stabilized on methadone were included. Methadone was measured by UPLC-MMS in serum and hemodialysates collected before morning methadone intake, every 30 minutes during 4 hours hemodialysis and before afternoon dose, and in urine sampled at the end of hemodialysis. ECGs were recorded every 30 minutes during hemodialysis, and QT time was measured in lead v2 using tangential method and QTc was calculated with Bazzet’s formula. ECGs were read serially for each patient with blinding of numbering. Several routine biochemical tests were performed before and after hemodialysis. The daily methadone dose was 100 (60–120) mg. Serum-methadone increased from Cmin of 1124 (547–1581) nmol/L to Cmax of 1806 (1237–2098) nmol/l after 85 (40–120) minutes. The apparent half-life of methadone was 12 (6.3–25) hours. A total of 2.30 (1.25–3.70) % and 0.14 (0.03–0.26) % of daily methadone intake was collected, respectively, in hemodialysate and urine during 4 hours. Renal clearance of methadone was 0.67 (0.31–1.20) mL/min, methadone clearance of hemodialysis was 17.10 (13.67–20.61) mL/min and AUC of dose interval was 253.5 mg min/L. QTc increased from 395 (369–406) ms to 452 (407–479) ms with P = 0.068,Wilcoxon paired comparison. The maximum QTc occurred 180 (135–219) min after methadone intake. QTc did not increase with increasing methadone concentrations, R2 = 0.0015. Another route than renal and hemodialysis must eliminate methadone in these patients as only a small amount of methadone was lost in hemodialysate and urine. All values of serum-methadone were comparable with those seen in patients with normal renal function after similar daily methadone doses. QTc tended to increase during hemodialysis. However, this increase was not concentration-dependent on methadone." @default.
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• W2011051663 date "2013-08-01" @default.
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• W2011051663 title "PP204—Methadone Kinetics and Corrected QT Time During Haemodialysis in Four Methadone Maintenance Treatment Patients with End-Stage Renal Failure" @default.
• W2011051663 doi "https://doi.org/10.1016/j.clinthera.2013.07.234" @default.
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