Pharmacokinetics of methadone during maintenance therapy: Pulse labeling with deuterated methadone in the steady state

Summary A technique is presented for study of steady state kinetics of methadone using pulse labeling with deuterated methadone (d₃) and mass fragmentography to measure both unlabeled and labeled methadone in blood. Seven subjects maintained on methadone for at least 10 months were admitted to a closed metabolic ward. The daily dose of unlabeled methadone (d₀) was substituted by one dose of methadone-d₃ and plasma levels of methadone-d₀ and methadone-d₃ were followed for 48 h using a precise (SD±5%) and sensitive (30 pmol/ml) mass fragmentographic technique. Plasma half-lives (t_1/2) for both methadone-d₀ and metadone-d₃ were calculated from samples obtained 8–24 h following the dose of methadone-d₃. The t_1/2 of oral methadone-d₃ was shorter (22±2 h) than that of methadone-d₀ (52±20 h). The same pattern was observed after intravenous administration. The results indicate multiple pools of methadone in the body.