Therapeutic drug monitoring in methadone maintenance: Choosing a matrix

Methadone maintenance is the premier pharmacological treatment for opioid a ddiction, but it is rarely informed by evidence-based practice guidelines f or dosage monitoring and adjustment. Such guidelines ale crucial because th e pharmacokinetics of methadone vary greatly among patients, and this varia tion may account for differences in treatment outcome. We review the pharma cokinetics of methadone and factors that may alter it (including drug inter actions, disease states, and idiosyncratic differences among patients). Als o 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, sa liva may be a promising matrix. However, saliva methadone concentrations ar e influenced by salivary pH, and future studies are needed to determine how to control for that. Administrative, medical, and social implications of m ethadone TDM are briefly discussed.