Comparative pharmacokinetics of nalbuphine nasal spray and solution for injection in healthy volunteers

Abstract

AbstractAimsNalbuphine is a synthetic opioid with comparable analgesic activity to morphine but with a better safety profile. Nalbuphine is only available in injectable form due to low oral bioavailability. Nasal nalbuphine spray provides advantages in drug safety, avoids hepatic first‐pass metabolism, is non‐invasive and is convenient for patient‐controlled analgesia by self‐administration. This study aimed to evaluate the safety and pharmacokinetics (PK) of the newly developed nalbuphine nasal spray in comparison with a solution for injections.MethodsTwenty‐four healthy Caucasian volunteers were enrolled in this randomized, open‐label, cross‐over study. Subjects were administered one of the drugs: nasal spray 7.0 mg/dose, nalbuphine hydrochloride solution for injection 10 mg/dose intravenously (IV) or intramuscularly (IM). High‐performance liquid chromatography–tandem mass spectrometry was used to determine nalbuphine concentrations.ResultsA comparison of PK profiles for IV, IM and intranasal (IN) routes of nalbuphine administration revealed a close similarity of absorption phases for nasal spray and IM injection. Differences between the mean Tmax and dose‐adjusted Cmax values for nasal spray and IM injection were statistically insignificant. The median values of the elimination rate constants and the terminal elimination half‐life following IV, IM and IN nalbuphine administration were similar. The mean absolute bioavailability of the nasal spray equalled 65.04%.ConclusionsThe similarity of PK parameters of IM‐injected nalbuphine solution and the nasal spray allows us to assume the latter is a feasible alternative to intramuscular nalbuphine injections appropriate for self‐administration and field environments for managing moderate and severe pain of various aetiologies.