Methadone, administered daily at a steady dose, should be present in the blood in levels sufficient to maintain "normalcy" over a 24-hour period. That is, the patient should not feel drugged or "high," or have withdrawal symptoms (abstinence syndrome) during that time.

Measuring levels of methadone in the blood-in terms of nanograms per milliliter or ng / mL - is helpful in determining how much of the medication is circulating in the patient's system. Typically, the blood level reaches a high point, or "peak," about 3 to 4 hours after taking the dose. There is a gradual decline over the remainder of the 24-hour period to a low point or "trough" level.

Blood levels are interpreted in the context of the patient's clinical presentation; the lab values help in making dosing decisions when faced with challenging cases. The trough level at 24 hours should be at least 150 to 200 ng/mL, or 400 ng/mL to achieve cross-tolerance, thereby making ordinary doses of IV heroin ineffective. [1]

In practice, serum methadone levels are sometimes more helpful in confirming inadequate dose than in determining optimum dose. Clinicians Sarz Maxwell, MD and Marc Shinderman, MD recommend that a minimum of 400 ng/mL (trough level) is usually effective for alleviating objective signs and subjective symptoms of opioid abstinence syndrome. [2]

The peak level at 3 to 4 hours should be no more than twice the trough level, giving an ideal peak/trough ratio of 2 or less. This rate-of-change ratio can be of more clinical value than the actual levels. A ratio of 3.5 would indicate rapid metabolism (early peaking) possibly leading to unexpected withdrawal symptoms, whereas 1.7 might suggest normal metabolism. A trough level alone, although useful, does not indicate the rate of change over the time-course of a dose. [1]

Methadone peak, trough, and average levels and the rate of elimination (half-life) may be influenced by several factors: metabolism, poor absorption, changes in urinary pH, concomitant medications or drug abuse, diet, physical condition, pregnancy, even vitamins. [1,3,4] Research also shows that two equally occurring forms of the methadone molecule (enantiomers) in the medication-one active, the other inactive- are metabolized at unequal rates in some patients. The amount of active methadone can vary greatly between two patients at the same serum level; one will be comfortable while the other is not. [2,5] However, the clinical utility of this has not yet been established and testing for the ratio of active to inactive methadone in serum is not commonly available.