|PEAKS AND TROUGHS|
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. 
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. 
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. 
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.