THERAPEUTIC MONITORING OF NALBUPHINE - TRANSPLACENTAL TRANSFER AND ESTIMATED PHARMACOKINETICS IN THE NEONATE

Nalbuphine, a mixed agonist-antagonist opiate, is commonly used as a s ystemic analgesic during labour. Recent reports of perinatal adverse e ffects prompted us to carry out therapeutic nalbuphine monitoring in o bstetric analgesia. Because data on fetomaternal transfer are scarce a nd the pharmacokinetics of this drug ill the neonate are largely unkno wn, we report data obtained from 28 parturients treated with nalbuphin e either intramuscularly and/or intravenously during labour. Plasma na lbuphine levels were measured by high-performance liquid chromatograph y (HPLC) with electrochemical detection. At delivery, 30-150 mill afte r maternal administration, nalbuphine concentrations ranged from 5.0 t o 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 wer e highly correlated to dose. The fetomaternal ratio was high: 0.74 and not correlated to the administered dose of nalbuphine. An estimated p lasma half-life of 4.1 h was calculated from two determinations in the neonate based on the assumption of a monoexponential decay of nalbuph ine concentrations. Apart from a flattening of the fetal heart rate tr acing in 54% of the cases, only one neonate had a low Apgar score at b irth. The apparent prolonged half-life of nalbuphine in the neonate in dicates the usefulness of an intramuscular injection of naloxone to pr event recurrence of cardiorespiratory depression due to nalbuphine adm inistration to the mother.