Methadone plasma levels in maintenance patients: the effect of dose omission

The stability of methadone plasma levels during steady drug intake and the effects of a single dose omission on the methadone plasma level, were studied in 3 reliable patients (Group I) and in a nonselected group of 11 clinic patients (Group II). The plasma levels of methadone were determined by gas-liquid chromatography. In Group I patients receiving an average dose of 1.13 mg/kg (range 0.45-1.6 mg/kg) little day to day variation was seen: the average plasma level was 0.358 ug/ml with a variance of +/- 3.6% measured in 4 different days. Forty-eight hours after the last dose (after omission of a single dose), methadone plasma levels declined on the average by 0.179 ug/ml which represents a 50% decrease form the preomission average level. In Group II patients during the presumed steady methadone intake (average dose 1.25 mg/kg, range 0.57-1.75 mg/kg), the average plasma level of methadone was 0.377 ug/ml with a variance of 48.5% measured in 4 different days. A fall in methadone plasma levels occurred mainly after weekends in some of the Group II patients suggesting possibly nonconsumption of the prescribed dose of medication. The rapid and substantial decline of methadone plasma levels following a single dose omission is apparently a parallel to the observed rapid loss of methadone induced cross tolerance.