The disposition and bioavailability of intravenous and oral nalbuphine in healthy volunteers.

The pharmacokinetics of intravenous and oral nalbuphine were studied in 24 healthy male volunteers ranging in age from 21 to 30 years. On separate test days over a five-week period, subjects received single doses of each of four different formulations of nalbuphine, with a one-week washout period between treatments: 10 mg intravenously administered over two minutes, 45 mg orally given as a solution, and 45 mg orally administered in two tablet formulations (formulation A and formulation B). Blood samples were collected over 48 hours postadministration, and plasma nalbuphine concentrations were determined by reversed-phase high-performance liquid chromatography (HPLC) with electrochemical detection. The mean nalbuphine plasma concentration five minutes after 10 mg intravenously was 53 ng/mL, and the half-life of nalbuphine with this route of administration was 2.3 hours. In contrast, mean maximum nalbuphine concentrations (Cmax) after the three orally administered preparations ranged from 14.4 to 15.5 ng/mL, and occurred 0.9 to 1.2 hours after dose administration. Mean elimination half-lives after administration of the three nalbuphine oral formulations were essentially identical, ranging from 6.9 to 7.7 hours. Nalbuphine plasma concentration curves decayed biexponentially regardless of route of administration or type of formulation. Absolute bioavailability of the orally administered forms of nalbuphine ranged from 16.4 to 17.4% and Cmax and AUC data further established the bioequivalence of the three oral formulations. The low absolute bioavailability and prolonged elimination half-life of nalbuphine associated with oral administration are likely due to extensive first-pass metabolism and enterohepatic circulation, respectively.