A randomized, double-blind study to compare the efficacy and safety of nalbuphine nasal spray and injectable solution in patients after orthopaedic interventions and traumatological procedures.

AIMS: Our previous 3-period crossover study in healthy volunteers comparing the pharmacokinetics of nalbuphine nasal spray Apain with parenteral nalbuphine solution demonstrated high bioavailability of the nasal spray and close similarity of pharmacokinetic profiles after intranasal and intramuscular administration, especially within 30 min postdose. The aim of the present study was a noninferiority assessment of nalbuphine nasal spray vs. intramuscular injection for pain relief in postoperative patients. METHODS: Ninety orthopaedic and traumatology patients were enrolled in this double-blind, randomized study of the effectiveness and tolerance of a single 10.5 mg dose of nalbuphine nasal spray vs. 10 mg intramuscular injection. The summed pain intensity difference (SPID0-6) calculated using visual analogue scale scores was the primary study endpoint. RESULTS: Of 90 subjects enrolled, the per-protocol efficacy population comprised 79 patients; 6 patients in the reference group and 5 patients in the test group were excluded due to remedication. The mean values of study endpoints with 95% confidence interval were as follows in reference and test groups, respectively: SPID0-6 = 228.08 (205.73-250.43) vs. 248.73 9 (225.83-271.63), time to pain relief onset = 0.28 h (0.25-0.31) vs. 0.27 h (0.25-0.29), duration of analgesia = 5.55 h (5.17-5.93) vs. 5.51 h (5.10-5.92), area under the curve = 119.30 (91.17-147.43) vs. 99.81 (74.52-107.10). No statistically significant differences were revealed. CONCLUSION: Nalbuphine nasal spray Apain has been proven to be a safe, noninvasive alternative to intramuscular nalbuphine to relieve severe postoperative pain. Designed for self-administration and dose-adjusting, the noncontrolled opioid analgesic nalbuphine spray can be used for patient-controlled analgesia in out-of-hospital, field and home settings.

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 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%. 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.