Pharmacokinetic comparison of nalbuphine with single injection and patient‐controlled analgesia mimic method in healthy Chinese volunteers

Abstract

Nalbuphine is a mu (μ) receptor partial antagonist/kappa (κ) receptor agonist analgesic and can be administered as a single injection or using patient-controlled analgesia (PCA) in the clinical setting. However, differences in the pharmacokinetics of the two administration methods are unclear. Here, a clinical trial was performed to compare the pharmacokinetic characteristics and superiority of nalbuphine with a single-injection or PCA-mimic method to provide a reference for the selection of an appropriate administration method. Twenty healthy individuals were divided into two groups and injected with 10mg nalbuphine intravenously using a single-injection or a PCA-mimic method (2mg once for five times with a 30-min interval). Blood samples were collected, and safety was investigated. The liquid chromatography-tandem mass spectrometry was adopted to determine the concentration of nalbuphine in plasma. The maximum concentration (Cmax ) and area under concentration-time curve (AUC0-t ) values of nalbuphine in the single-injection and PCA groups were as follows: Cmax , 81.3±24.7 and 39.8±6.4ng/ml, respectively; moreover, AUC0-t , 110.3±19.5 and 128.3±23.0hng/ml, respectively. The effective analgesic concentration durations (EACDs) for the two administration methods were 1.39±0.64 and 1.96±0.91h, respectively. Nalbuphine was well tolerated, and improvements were observed in the PCA group. Compared with those in the single-injection group, the AUC0-t and EACDs in the PCA group were similar, whereas Cmax was decreased significantly. Therefore, the PCA method was more suitable for the clinical application of nalbuphine injection owing to the superiority of lower concentration fluctuation and the improved safety profile.