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

AIMS

Nalbuphine 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.

METHODS

Twenty-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.

RESULTS

A 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 T and dose-adjusted C 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%.

CONCLUSIONS

The 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.