Thrasher Research Fund - Medical research grants to improve the lives of children

Project Details

Early Career

Status: Funded - Closed

Liposomal Bupivacaine Pharmacokinetics and Breast Milk Excretion After Cesarean Delivery

Hiba Mustafa, MD

Summary

BACKGROUND: 1 in 300 opioid-naive patients exposed to opioids after cesarean birth are estimated to become persistent users of opioids. The rising prevalence of opioid use in pregnancy has led to a sharp increase in neonatal abstinence syndrome from 1.5 cases per 1,000 hospital births in 1999 to 6.0 per 1,000 hospital births in 2013. Liposomal bupivacaine can provide optimal pain control up to 96 hours following wound infiltration. GAP: Liposomal bupivacaine pharmacokinetics, milk excretion, and infant safety data are lacking. HYPOTHESIS: Post cesarean section liposomal bupivacaine wound infiltration can help significantly reduce chronic postpartum pain disorder that historically led to increased rates of chronic opioids use in pregnancy and neonatal abstinence syndrome. METHODS: Prospective pharmacokinetic study. Healthy pregnant women, aged 18-40, scheduled for term CD (37-42 weeks gestation) followed by TAP block using 52 mg bupivacaine hydrochloride (HCL) 0.25% (20ml) and 266 mg liposomal bupivacaine 1.3% (20 ml). Simultaneous blood and milk samples were collected in a staggered fashion 3-4 samples per patient at the following time-points following TAP block administration: 2h, 6h, 12h, 24h, 48h, 72h, and 96h. Quantification of bupivacaine in the collected blood and milk samples was performed by liquid chromatography- tandem mass spectrometry (LC-MS/MS). Infant’s drug exposure was modeled by calculating milk/plasma area under the curve (AUC) ratios, Infant Dosage (ID), and Relative Infant dosage (RID) of bupivacaine at each sampling time. RESULTS: Total of 30 healthy pregnant women were enrolled. Concentrations in breast milk peaked at 6h (57.98 ng/ml) followed by constant and steady decline to low levels at 96h (5.22 ng/ml). Maternal plasma concentrations had 2 peaks, first at 6h (155.87 ng/ml) and then at 24h (225.75 ng/ml) followed by steady decline. Milk/plasma (M/P) AUC0-t ratios ranged between AUC0-2 of 0.45 (80% CI: 0.38-0.52) and AUC0-96 of 0.15 (80% CI: 0.14-0.17). ID ranged between 355.9 at 0-2h and 15155.4 ng/kg at 0-96h time-intervals. RID was <1% at all-time intervals. No serious adverse reactions occurred in any infant and no clinically significant changes were found during the study’s follow up period of 14 days. IMPACT: The study will provide Anesthesiologists and Obstetricians the evidence they need to counsel women on medication safety in breast-feeding, and in implementing liposomal bupivacaine use in their practice as a reliable, safe alternative to opioids in managing postpartum pain.

Supervising Institution:
University of Minnesota

Mentors
Michael Todd

Project Location:
Minnesota

Award Amount:
$26,750