PHARMACOKINETICS OF INTRARECTAL NALBUPHINE IN CHILDREN UNDERGOING GENERAL-ANESTHESIA

The pharmacokinetics of nalbuphine (0.3 mg/kg) administered by the rec tal route were studied in ten children undergoing general anaesthesia for minor surgery. Blood sampling was carried out for 8 h after rectal administration and plasma drug concentrations were measured by high p erformance liquid chromatography using electrochemical detection after an optimized solid-phase extraction procedure. The mean time to achie ve the maximum plasma concentration (C-max = 24 +/- 15 ng/mL) was 25 /- 11 min and the elimination half-life was 2.7 +/- 0.7 h. The coeffic ients of variation for C-max and the concentration-time curve (AUC) we re 62 and 68%, respectively. Although rectal absorption is considered irregular, the large intersubject variability is also explainable by a variable hepatic bypass for a drag, like nalbuphine, that undergoes e xtensive first-pass metabolism. No problem of analgesic efficacy or of local tolerance was reported. In conclusion, the rectal route of admi nistration provides a rapid and reliable absorption of nalbuphine.