Pharmacokinetics of Oral and Extended-release Naltrexone in Pregnant and Lactating Individuals and their Infants.

Abstract

Naltrexone may be utilized for the treatment of opioid and/or alcohol use disorder during pregnancy. However, limited information is available on the pharmacokinetics of naltrexone during pregnancy and lactation. The objective of this study was to evaluate maternal and infant concentrations of naltrexone and its major metabolite 6β-naltrexol in relevant matrices across pregnancy and the immediate postpartum period. Pregnant individuals receiving naltrexone were enrolled in this prospective cohort study. Maternal plasma and urine samples were collected serially during pregnancy at up to 6 time points. At delivery, cord blood, maternal plasma, infant plasma, and infant urine were collected. Four weeks after delivery, breastmilk, maternal plasma, and infant plasma samples were collected. All samples were analyzed for naltrexone and 6β-naltrexol using a validated liquid chromatography tandem mass spectrometry assay. A total of 7 pregnant individuals were enrolled: 4 receiving extended-release and 3 receiving oral naltrexone. Concentrations of naltrexone in maternal plasma in pregnancy remained detectable across the dosing interval for both formulations. The ratio of median cord blood to maternal plasma concentration was 1.11 in the extended-release and 0.74 in the oral group. Of the 7 infants, 1 remained breastfed at 4 weeks. The relative infant naltrexone dose via breastmilk at 31 days after delivery from the 1 infant was 0.83%. While limited due to sample size, these data provide valuable information about the pharmacokinetics of prenatal use of naltrexone and perinatal transfer, guiding counseling and clinical management of the parent-infant dyad.