Lopinavir/ritonavir treatment increases the placental transfer of bupivacaine enantiomers in human immunodeficiency virus-infected pregnant women

Abstract

Aims: The present study evaluated the placental transfer and amniotic fluid distribution of bupivacaine enantiomers in health pregnant women and in human immunodeficiency virus (HIV)-infected pregnant women receiving epidural anaesthesia for caesarean section. Methods: Twelve HIV-infected pregnant women (HIV group) were treated long-term (at least 8 weeks) with lopinavir/ritonavir (400/100 mg twice daily), and 12 healthy pregnant women (Control group) who submitted to epidural anaesthesia with racemic bupivacaine (75 mg) during caesarean section were investigated. At delivery, samples of maternal and fetal blood and amniotic fluid were collected (10–20 min after drug administration). Results: The placental transfer ratio of bupivacaine enantiomers was significantly higher among the pregnant women from the HIV group when compared with those from the Control group (Mann–Whitney test, P ≤ 0.05). Placental transfer ratios (median and 25th - 75th percentiles) for (+)-(R)-bupivacaine were 0.58 (0.38–0.82) in the HIV group vs. 0.25 (0.18–0.33) in the Control group, and for (–)-(S)-bupivacaine, they were 0.54 (0.34–0.69) in the HIV group vs. 0.25 (0.19–0.29) in the Control group. The transplacental distribution of bupivacaine was stereoselective only in the HIV group. The umbilical artery/umbilical vein ratio and amniotic fluid/maternal vein ratio were low and nonstereoselective, and no statistically significant differences were observed between the groups. Conclusions: This study supports that the placental transfer of both bupivacaine enantiomers was 100% higher in HIV-pregnant women treated with lopinavir/ritonavir when compared with that in healthy pregnant women receiving epidural anaesthesia for caesarean section.