Buprenorphine exposure in infants of opioid-dependent mothers at birth
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Background: Buprenorphine, a partial opioid agonist used in treating opioid dependence, is not approved in Australia for use in pregnancy. Nevertheless, many pregnant women choose to remain on the drug. Aim: To investigate cord/maternal transfer ratios for buprenorphine and norbuprenorphine in women at delivery. Methods: Maternal and cord serum samples were collected from 10 maternal-infant pairs at delivery. Drug concentrations were measured by liquid chromatography-tandem mass spectrometry. Maternal and infant demographic information was collected. Linear regression was used to assess the relationship between maternal and cord measurements. Results: Median (interquartile range) maternal age was 27 (23.8–32) years, with 90% of the women on buprenorphine before pregnancy. Median infant birthweight was 3148 (3088–3545) g and 60% of infants had neonatal abstinence requiring admission to a neonatal intensive care unit for a median of 8.5 (2.5–16.3) days. Median maternal buprenorphine daily dose was 8.5 mg (range 1–28 mg). Mean (95% confidence interval) cord serum concentrations of buprenorphine and norbuprenorphine were 0.4 (0.3–0.5) μg/L and 1.2 (0.9–1.4) μg/L, respectively. Mean maternal concentrations of buprenorphine and norbuprenorphine were 1.0 (0.6–1.4) μg/L and 1.2 (0.9–1.4) μg/L, respectively. Mean cord/maternal ratios were 0.43 (0.36–0.5) for buprenorphine and 0.53 (0.43–0.63) for norbuprenorphine. Maternal buprenorphine and norbuprenorphine concentrations and ratio of buprenorphine/norbuprenorphine explained 85.7, 69.6 and 94.4%, respectively, of variation in the corresponding cord concentrations. Conclusion: Usual therapeutic doses of buprenorphine administered to pregnant women resulted in low concentrations of buprenorphine and norbuprenorphine in maternal serum and a low transfer to the fetal circulation (cord plasma) at birth.
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