Evaluation of Analgesic Patches in Cynomolgus Macaques (Macaca fascicularis)

Opioids are widely used in veterinary and human medicine to manage pain. However, there is a paucity of information in the literature regarding the pharmacokinetics of opioid transdermal patches (TDP) in NHP. Therefore, to determine whether opioid TDP attain therapeutic concentrations in NHP, the pharmacokinetics of fentanyl (25 μg/h) and buprenorphine (10 and 20 μg/h) TDP were evaluated in naïve, adult, male cynomolgus macaques (n = 4) in a crossover study. Plasma opioid levels were determined by tandem liquid chromatography-mass spectrometry. The AUC_0-inf for fentanyl and the low and high dose buprenorphine patches were 115 ± 14, 462 ± 74, and 778 ± 344 ng× h/mL, and the plasma half-lifes were 22 ± 4, 77 ± 27, and 42 ± 11 h, respectively. No adverse effects were noted throughout the study. Minimal therapeutic concentrations for fentanyl (0.2 ng/mL) and buprenorphine (0.1 ng/mL) were achieved in all macaques within 8 h of fentanyl and 24 h of buprenorphine TDP application. Therapeutic levels for the fentanyl and low- and high-dose buprenorphine patches were maintained for 96, 120, and 144 h, respectively. These findings suggest that 25-μg/h fentanyl patches should be replaced every 4 d, and the low- and high-dose buprenorphine patches should be replaced every 5 and 6 d, respectively. The results of this study show that fentanyl and buprenorphine patches achieve minimal therapeutic levels for clinically relevant periods of time and should be considered viable options for pain management in cynomolgus macaques.