Clinical Information Discusses physiology, pathophysiology, and general clinical aspects, as they relate to a laboratory test
Methadone (Dolophine) is an opioid receptor agonist with analgesic and pharmacologic properties similar to morphine. It can be administered orally and provides analgesia for approximately 24 hours. The I-racemate of the drug is active, while the d-racemate has little activity. Methadone has properties that make it useful for treating heroin addiction. Sedation ensues with higher doses, which is an undesirable side effect. Administered in small doses of 5 to 20 mg, the drug occupies the opioid receptor for prolonged periods of time, blocking the action of morphine, precluding the euphoric effect that heroin addicts seek. Addicts who self-administer heroin while taking methadone experience no effect from the heroin, and addicts who take large methadone doses do not experience euphoria, only sedation, miosis, respiratory depression, hypotension, and dry-mouth. Tolerant patients may require doses of 60 to 100 mg per day.
Methadone is metabolized by demethylation (cytochrome P 2D6 [CyP 2D6]) to 2-ethylidene-1,5-dimethyl-3,3-diphenylpyrrolidine and to 2-ethyl-5-methyl-3,3-diphenylpyrrolidinr. Individuals with genetic deficiencies of CyP 2D6 or those who are coadministered amiodarone, paroxetine, protease inhibitor antiretrovirals, chlorpheniramine, or other drugs that inhibit CyP 2D6 will accumulate methadone and be at risk for associated toxicity.
Compliance monitoring of methadone therapy in patients being treated for heroin addiction
The minimal effective serum concentration for analgesia is 30 ng/mL. Peak therapeutic serum concentrations of 30 to 90 ng/mL occur 4 hours after dose. Patients continuously administered methadone develop tolerance and have higher serum concentrations than indicated by the reference range; these patients may tolerate concentrations up to 400 ng/mL. Methadone concentrates in serum; the ratio of blood to serum methadone is 0.75.
Cautions Discusses conditions that may cause diagnostic confusion, including improper specimen collection and handling, inappropriate test selection, and interfering substances
Because methadone has a wide therapeutic index and dose-dependent toxicity, routine drug monitoring is not indicated in all patients.
Reference Values Describes reference intervals and additional information for interpretation of test results. May include intervals based on age and sex when appropriate. Intervals are Mayo-derived, unless otherwise designated. If an interpretive report is provided, the reference value field will state this.
Single dose: 30-90 ng/mL
Maintenance dose: 400-1,000 ng/mL
Clinical References Provides recommendations for further in-depth reading of a clinical nature
1. Goodman LS, Gillman A, Hardman JG, et al: The pharmacological basis of therapeutics. Ninth edition. Edited by JG Hardman, LE Limbird. New York, McGraw-Hill Book Company, 1996, pp 544-555
2. Baselt RC: Disposition of toxic drugs and chemicals in man. Fifth edition. Foster City, CA, Chemical Toxicology Institute, 2000, pp 523-527