Alterations in methadone metabolism during late pregnancy

Traditionally, methadone maintenance therapy has been a once-daily dosing s chedule. The current study evaluates the effectiveness of this regimen duri ng pregnancy. A total of 23 pregnant and 16 non-pregnant opioid-dependent p atients were studied in two phases to evaluate pregnancy-dependent changes in methadone pharmacokinetics. In the first phase, pregnant patients had a statistically significant higher elimination rate constant (k) and lower ha lf-life compared to non-pregnant controls. In the second phase, the apparen t clearance (Cl/F) was significantly greater during pregnancy, with prelimi nary data suggesting that this observation results from a decrease in the f raction of dose absorbed (F). The implications of these findings on dosing regimens during pregnancy is discussed.