|INTERPRETATION OF METHADONE BLOOD LEVELS|
Reference Range: 100-1000ng/mL
Therapeutic monitoring of serum methadone values is based on the patient reaching a steady state of methadone values by dosing with the same milligram dosage for 5 to 6 days. Relative steady state concentrations should be achieved during this time. The pre-dose value (TROUGH) is the lowest serum value for the patient and is measured on a sample drawn just prior to daily dose. The post-dose value (PEAK) is the concentration of a serum sample drawn 4 hours after the dose. Ideally the values should be very nearly the same. This indicates that the methadone absorbed by the patient in the daily dose is distributed uniformly throughout the vascular and organ storage volume of the body. The methadone is then available at a uniform rate at the opiod receptor binding sites. When the pre-dose (TROUGH) and the post-dose (PEAK) values differ greatly, there is an increased metabolism and excretion by the patient. This may result in the patient's claim of withdrawal. Dose timing and/or increase should be considered as options.
Relation of Methadone Dosage to Serum Concentrations
Pre-dose values (TROUGH): As an approximation the relationship of serum values to dosage is 263 ng/mL for every milligram of methadone consumed per kilogram of body weight. This assumes normal hydration, the absence of liver disease and any other drug interactions.
Post-dose 4 hours (PEAK): The half-life for methadone in plasma is 15-55 hours. This is the time for 50% of the dose to be metabolized and excreted in the urine. Using 24 hours as the half-life, one can very easily estimate the PEAK value as being two times the TROUGH value. However, the most important factor in evaluating the PEAK concentration is the difference in magnitude between the PEAK and TROUGH. If the difference is very great this indicates that the patient is experiencing a change in the physiological effect of the drug. The patient would probably be experiencing withdrawal symptoms late in the day. Splitting or increasing the dose might be considered for these patients
Useful Information and Calculations
Table 1. Patient samples analyzed for PEAK and TROUGH levels of methadone.
Meth Conc.= 263ng/mL (Dose, mg/d)/Wgt(Kg) (1.)
Plasma Half-Life: 15 to 55 Hours
Major metabolites: EDDP and EMDP