Therapeutic monitoring of nalbuphine: transplacental transfer and estimated pharmacokinetics in the neonate

Abstract

Nalbuphine, a mixed agonist-antagonist opiate, is commonly used as a systemic analgesic during labour. Recent reports of perinatal adverse effects prompted us to carry out therapeutic nalbuphine monitoring in obstetric analgesia. Because data on fetomaternal transfer are scarce and the pharmacokinetics of this drug in the neonate are largely unknown, we report data obtained from 28 parturients treated with nalbuphine either intramuscularly and/or intravenously during labour. Plasma nalbuphine levels were measured by high-performance liquid chromatography (HPLC) with electrochemical detection. At delivery, 30-150 min after maternal administration, nalbuphine concentrations ranged from 5.0 to 79.2 ng.ml-1 in mother plasma samples and from 3.0 to 46.6 ng.ml-1 in umbilical cord plasma samples. Nalbuphine concentrations were highly correlated to dose. The fetomaternal ratio was high: 0.74 and not correlated to the administered dose of nalbuphine. An estimated plasma half-life of 4.1 h was calculated from two determinations in the neonate based on the assumption of a monoexponential decay of nalbuphine concentrations. Apart from a flattening of the fetal heart rate tracing in 54% of the cases, only one neonate had a low Apgar score at birth. The apparent prolonged half-life of nalbuphine in the neonate indicates the usefulness of an intramuscular injection of naloxone to prevent recurrence of cardiorespiratory depression due to nalbuphine administration to the mother.

Population pharmacokinetics of nalbuphine after surgery in children

“…Although nalbuphine has been approved for clinical use in children, pharmacokinetic data of the drug remain very limited. Nicolle and colleagues 7 reported data for a few neonates whose mothers had received nalbuphine during labour. Jacqz-Aigrain and colleagues 8 have reported data of a population pharmacokinetic study carried out in neonates.…”

Maternal and neonatal effects of nalbuphine given immediately before induction of general anesthesia for elective cesarean section

“…Nalbuphine pass through the placenta rapidly[1213] and the elimination half-life of nalbuphine in neonates is 4.1 hours,[14] which was shorter than that of meperidine in neonates 7-32 hours. [15] So, the neonatal effects of nalbuphine will be of shorter duration than meperidine.…”

“…[14] to delineate placental transfer and disposition of nalbuphine in the neonate found that nalbuphine placental transfer is high and estimated half life of nalbuphine in neonate is longer than in adult and two neonates had low APGAR score at one minutes and one of them had score of 8, which improved spontaneously to 10 at 5 min and the other had score 3 and improved to 10 after resuscitation.…”

Nalbuphine: a candidate for treatment of women overwhelmed with sudden, intense labor pain?

“…Nalbuphine was introduced as a systemic obstetric analgesic in the 1980s, and its safety profile presented also as such an advantage over other opioids that are also known to cross the placental barrier [3,6]. In modern obstetric anesthesia, nalbuphine plays only a neglectable role.…”