TY - JOUR
T1 - Bupivacaine Pharmacokinetics and Breast Milk Excretion of Liposomal Bupivacaine Administered after Cesarean Birth
AU - Mustafa, Hiba J.
AU - Wong, Henry L.
AU - Al-Kofahi, Mahmoud
AU - Schaefer, Malinda
AU - Karanam, Ashwin
AU - Todd, Michael M.
N1 - Publisher Copyright:
© 2020 Lippincott Williams and Wilkins. All rights reserved.
PY - 2020/7
Y1 - 2020/7
N2 - OBJECTIVE:To evaluate bupivacaine concentrations in maternal plasma and transfer into breast milk in women undergoing liposomal bupivacaine infiltration in the transversus abdominis plane after cesarean birth.METHODS:Prospective cohort study of healthy pregnant women who underwent cesarean birth at term followed by a transversus abdominis plane block using 52 mg bupivacaine hydrochloride 0.25% (20 mL) and 266 mg liposomal bupivacaine 1.3% (20 mL). Simultaneous blood and milk samples were collected in a staggered fashion, three to four samples per patient at the following timepoints after block administration: 2, 6, 12, 24, 48, 72, and 96 hours. Quantification of bupivacaine was performed by liquid chromatography-tandem mass spectrometry. Neonatal drug exposure was modeled by calculating milk/plasma area under the curve (AUC) ratios, neonatal dosage, and relative neonatal dosage of bupivacaine at each sampling time.RESULTS:Thirty patients were enrolled. Concentrations in breast milk peaked at 6 hours (mean 58 ng/mL), followed by constant and steady decline to low levels at 96 hours (mean 5.2 ng/mL). Maternal plasma concentrations had two peaks, first at 6 hours (mean 155.9 ng/mL) and then at 48 hours (mean 225.8 ng/mL), followed by steady decline. Milk/plasma AUC0-tratios ranged between AUC0-2of 0.45 (80% CI 0.38-0.52) and AUC0-96of 0.15 (80% CI 0.14-0.17). Neonatal dosage ranged between a mean of 355.9 ng/kg at 0-2 hours and a mean of 15,155.4 ng/kg at 0-96 hours. Relative neonatal dosage was less than 1% at all time intervals. No serious adverse reactions occurred in any neonate.CONCLUSION:Bupivacaine is excreted in breast milk after local infiltration of liposomal bupivacaine and bupivacaine hydrochloride mixture into transversus abdominis plane blocks after cesarean birth. Relative neonatal dosages of less than 1% (less than 10% is considered to be unlikely to be of clinical concern) suggest minimal risks for breastfeeding healthy, term neonates after the administration of this combination of local anesthetics to mothers.CLINICAL TRIAL REGISTRATION:ClinicalTrials.gov, NCT03526419.
AB - OBJECTIVE:To evaluate bupivacaine concentrations in maternal plasma and transfer into breast milk in women undergoing liposomal bupivacaine infiltration in the transversus abdominis plane after cesarean birth.METHODS:Prospective cohort study of healthy pregnant women who underwent cesarean birth at term followed by a transversus abdominis plane block using 52 mg bupivacaine hydrochloride 0.25% (20 mL) and 266 mg liposomal bupivacaine 1.3% (20 mL). Simultaneous blood and milk samples were collected in a staggered fashion, three to four samples per patient at the following timepoints after block administration: 2, 6, 12, 24, 48, 72, and 96 hours. Quantification of bupivacaine was performed by liquid chromatography-tandem mass spectrometry. Neonatal drug exposure was modeled by calculating milk/plasma area under the curve (AUC) ratios, neonatal dosage, and relative neonatal dosage of bupivacaine at each sampling time.RESULTS:Thirty patients were enrolled. Concentrations in breast milk peaked at 6 hours (mean 58 ng/mL), followed by constant and steady decline to low levels at 96 hours (mean 5.2 ng/mL). Maternal plasma concentrations had two peaks, first at 6 hours (mean 155.9 ng/mL) and then at 48 hours (mean 225.8 ng/mL), followed by steady decline. Milk/plasma AUC0-tratios ranged between AUC0-2of 0.45 (80% CI 0.38-0.52) and AUC0-96of 0.15 (80% CI 0.14-0.17). Neonatal dosage ranged between a mean of 355.9 ng/kg at 0-2 hours and a mean of 15,155.4 ng/kg at 0-96 hours. Relative neonatal dosage was less than 1% at all time intervals. No serious adverse reactions occurred in any neonate.CONCLUSION:Bupivacaine is excreted in breast milk after local infiltration of liposomal bupivacaine and bupivacaine hydrochloride mixture into transversus abdominis plane blocks after cesarean birth. Relative neonatal dosages of less than 1% (less than 10% is considered to be unlikely to be of clinical concern) suggest minimal risks for breastfeeding healthy, term neonates after the administration of this combination of local anesthetics to mothers.CLINICAL TRIAL REGISTRATION:ClinicalTrials.gov, NCT03526419.
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U2 - 10.1097/AOG.0000000000003886
DO - 10.1097/AOG.0000000000003886
M3 - Article
C2 - 32541292
AN - SCOPUS:85087320625
SN - 0029-7844
VL - 136
SP - 70
EP - 76
JO - Obstetrics and gynecology
JF - Obstetrics and gynecology
IS - 1
ER -