Altered methadone pharmacokinetics in pregnancy: implications for dosing.

Lower plasma methadone levels have been reported in pregnant women receiving methadone maintenance for heroin addiction. Methadone pharmacokinetics was examined in a 24-year-old woman 8 months pregnant with twins, who experienced severe withdrawal symptoms beginning 10-12 hours after her daily 30 mg methadone dose. Methadone plasma concentration-time data were fit to a one-compartment pharmacokinetic model by extended least-squares regression. Estimated half-life for methadone was 8.1 hours, which is much shorter than the usual methadone half-life (greater than 24 hours). Plasma methadone concentrations were estimated for the cases of a) increasing the 30 mg methadone dose by 50% and administering it once daily and b) continuing the 30 mg methadone dose but administering it at 12-hour intervals. Although the model is derived from a single subject, the simulations performed clearly suggest a need for altered methadone dosing in pregnancy. More sustained plasma methadone levels are achieved with twice-daily dosing of methadone than are achieved by administering an increased methadone dose once daily. Twice-daily dosing would be expected to produce fewer withdrawal symptoms and, ultimately, improved compliance with treatment.