Eddp [HRP]

OBJECTIVE. In a sample of methadone-maintained breastfeeding women and a matched group of formula-feeding women, this study evaluated concentrations of methadone in breast milk among breastfeeding women and concentrations of methadone in maternal and infant plasma in both groups. METHODS. Eight methadone-maintained (dose: 50-105 mg/day), lactating women provided blood and breast milk specimens on days 1, 2, 3, 4, 14, and 30 after delivery, at the times of trough and peak maternal methadone levels. Paired specimens of foremilk and hindmilk were obtained at each sampling time. Eight matched formula-feeding subjects provided blood samples on the same days. Infant blood samples for both groups were obtained on day 14. Urine toxicological screening between 36 weeks of gestation and 30 days after the birth confirmed that subjects were not using illicit substances in the perinatal period. RESULTS. Concentrations of methadone in breast milk were low (range: 21.0-462.0 ng/mL) and not related to maternal dose. There was a significant increase in methadone concentrations in breast milk over time for all 4 sampling times. Concentrations of methadone in maternal plasma were not different between groups and were unrelated to maternal dose. Concentrations of methadone in infant plasma were low (range: 2.2-8.1 ng/mL) in all samples. Infants in both groups underwent neurobehavioral assessments on days 3, 14, and 30; there were no significant effects of breastfeeding on neurobehavioral outcomes. Fewer infants in the breastfed group required pharmacotherapy for neonatal abstinence syndrome, but this was not a statistically significant finding. CONCLUSION. Results contribute to the recommendation of breastfeeding for methadone-maintained women.

To examine the effect of a single oral dose of methadone on cytochrome P450 (CYP) 3A activity using the urinary 6 beta -hydroxycortisol to cortisol ratio (UCR) as a marker of CYP3A activity. Methods A single oral dose (0.2 mg kg(-1)) of rac-methadone was administered to eight healthy female volunteers. Frequent blood samples and all urine over seven time periods was collected For 96 h following dosing. The UCR and the concentration of the major CYP3A metabolite of methadone, EDDP, were measured in urine. Methadone enantiomer concentrations were determined in plasma and urine. All quantifications were performed by validated high performance liquid chromatography assays. Results In all Volunteers a significant decline of the UCR from immediately predose values was observed at the 4-8 and 8-12 h collection periods (P < 0.05, 95% CI for the differences. 0.4.16 and 0.6.16, respectively) with a return to immediately predose values after 2-3 days, suggesting methadone was an inhibitor of CYP3A. The UCR was found to be significantly correlated with the amount of EDDP excreted in the urine and with the area under the plasma concentration vs time profile for total (R + S) methadone supporting in vitro data that CYP3A is primarily responsible for EDDP formation and has a significant influence on methadone disposition. Conclusions Methadone appears to be a CYP3A inhibitor in vivo following a single oral dose and measurements of the urinary cortisol ratio appear to be a useful index to follow this inhibition.