Therapeutic drug monitoring in methadone maintenance: choosing a matrix.
Methadone maintenance is the premier pharmacological treatment for opioid addiction, but it is rarely informed by evidence-based practice guidelines for dosage monitoring and adjustment. Such guidelines are crucial because the pharmacokinetics of methadone vary greatly among patients, and this variation may account for differences in treatment outcome. We review the pharmacokinetics of methadone and factors that may alter it (including drug interactions, disease states, and idiosyncratic differences among patients). Also reviewed are prospects for therapeutic drug monitoring (TDM) of methadone in plasma, urine, sweat, and saliva. Due to its ease of collection and its presumed representation of the bioavailable free-fraction of methadone, saliva may be a promising matrix. However, saliva methadone concentrations are influenced by salivary pH, and future studies are needed to determine how to control for that. Administrative, medical, and social implications of methadone TDM are briefly discussed.
Moolchan
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Department of Health and Human Services, National Institute of Health, National Institute of Drug Abuse, Baltimore, MD 21224, USA. emoolcha@intra.nida.nih.gov
Umbricht
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A
Epstein
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D051544:Cytochrome P-450 CYP3A; D003577:Cytochrome P-450 Enzyme System / Q000378:metabolism; D004347:Drug Interactions; D016903:Drug Monitoring; D005260:Female; D006207:Half-Life; D006801:Humans; D008099:Liver / Q000378:metabolism; D008297:Male; D008691:Methadone / Q000378:metabolism / Q000493:pharmacokinetics / Q000627:therapeutic use*; D006899:Mixed Function Oxygenases / Q000378:metabolism; D009294:Narcotics / Q000378:metabolism / Q000493:pharmacokinetics / Q000627:therapeutic use*; D009293:Opioid-Related Disorders / Q000534:rehabilitation*; D012463:Saliva / Q000378:metabolism; D013542:Sweat / Q000378:metabolism
D009294:Narcotics; D003577:Cytochrome P-450 Enzyme System; D006899:Mixed Function Oxygenases; C104464:CYP3A protein, human; D051544:Cytochrome P-450 CYP3A; D008691:Methadone