Methadone Peak Level, Serum or Plasma

Methadone possesses many of the pharmacologic properties of morphine and is approximately equipotent as an analgesic when administered parenterally. Unlike morphine, however, methadone produces marked sedative effects with repeated administration as a result of drug accumulation. This undesirable property restricted clinical usage of the drug until 1965 when Dole and Nyswander began narcotic maintenance treatment of former heroin addicts using large daily oral doses of dl-methadone.¹ Whereas maintenance patients may receive as much as 180 mg of the drug daily, doses of ≤50 mg have been known to prove fatal to nontolerant adults. The pharmacologic activity is due almost entirely to the l-isomer. The d-methadone isomer does have analgesic properties in large doses and this may be due to conversion to minor amounts of α-1-methadone and α-1-normethadol, both of which are potent analgesics. Methadone can be detected in blood 15 to 45 minutes after oral administration, with peak levels occurring at 2.5 to 4 hours. The elimination of half-life has a mean value of approximately 22 hours (range 5 to 130 hours). Due to interindividual variation of P450 enzyme systems, a 17-fold variation in methadone blood concentrations can be found in patients given the same dose.² The rate-of-change ratio between peak and trough SML measures can be a more clinically useful guide, and it has been suggested that the peak SML should be more than twice the trough level.³