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Pharmacokinetics of methadone and its primary metabolite in 20 opiate addicts

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In a closed metabolic ward the pharmacokinetics of methadone and its primary metabolite (EDDP) were studied in 20 long-term opiate addicts. After administration of the daily oral dose of methadone HCl (mean 60 mg, range 10–225 mg) blood samples were taken and analysed, using a newly developed high-performance liquid chromatography (HPLC) method. The steady-state plasma concentrations of the 20 subjects varied from 65–630 ng·ml−1 and from 5 to 55 ng·ml−1, whereas the peak concentrations were 124–1255 ng·ml−1 and 10 – 301 ng·ml−1 for methadone and EDDP, respectively. The calculated ratios between the area under the curve (AUC(0–24 h)) for methadone and the AUC(0–24 h) for EDDP varied from 5.9 to 44.6, indicating interindividual differences in metabolic activity. In 19 out of 20 subjects the pharmacokinetics of methadone are best described using a two-compartment model. The mean body clearance was 1.64 ml·min−1·kg−1, whereas the mean elimination rate constant (β) and plasma half-life (t 1/2β) were 0.026·h−1 (range 0.013–0.053·h−1) and 31.2 h (range 13–53 h), respectively. Differences of gender were also found. A poor correlation was found between the methadone dose and the steady-state level. A much better correlation was found between the normalized steady-state level and the body clearance.

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Correspondence to J. G. R. Ufkes.

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de Vos, J.W., Ufkes, J.G.R., van Wilgenburg, H. et al. Pharmacokinetics of methadone and its primary metabolite in 20 opiate addicts. Eur J Clin Pharmacol 48, 361–366 (1995). https://doi.org/10.1007/BF00194951

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Key words

  • Methadone
  • Opiate addicts
  • methadone metabolite
  • steady-state pharmacokinetics
  • one-compartment model
  • two-compartment model