Pharmacokinetics and Safety of Oxycodone/Naloxone Prolonged-Release Tablets in Chinese Patients with Chronic Pain

The study aimed to assess pharmacokinetics and safety of two oxycodone/naloxone prolonged-release tablet formulations in the Chinese population.

The study was conducted in 36 Chinese patients with chronic pain in both fasting and fed states. Each state involved a single-dose (40 mg/20 mg), randomized, open-label, two-period crossover clinical trial.

In the fasting study, the mean (± standard deviation, SD) peak concentration (C_max), area under concentration-time curve from time 0 to the last measurable concentration (AUC_0-t) and to infinite time (AUC_0-∞), and elimination half-life (t_1/2) of oxycodone for the brand-name and generic formulations were 50.9 ± 10.9 and 52.1 ± 9.58 ng/mL, 577 ± 148 and 554 ± 104 h*ng/mL, 579 ± 150 and 556 ± 104 h*ng/mL, and 5.17 ± 0.834 and 5.10 ± 0.877 h, respectively. Both median time to C_max (T_max) were 2.00 h. Parameters of naloxone and its main metabolite naloxone-3β-D-glucuronide were C_max 89.3 ± 20.6 and 85.6 ± 23.4 ng/mL, AUC_0-t 547 ± 104 and 538 ± 131 h*ng/mL, AUC_0-∞ 552 ± 104 and 543 ± 133 h*ng/mL, and t_1/2 6.59 ± 1.77 and 6.00 ± 1.88 h. Both T_max were 1.00 h. In the fed study, for oxycodone, parameters were C_max 71.2 ± 10.2 and 82.3 ± 17.1 ng/mL, AUC_0-t 697 ± 171 and 696 ± 154 h*ng/mL, AUC_0-∞ 699 ± 173 and 698 ± 155 h*ng/mL, and T_max 2.50 and 3.50 h. Both t_1/2 were similar to those in the fasting study. Naloxone and naloxone-3β-D-glucuronide showed similar parameters to those in the fasting study except for T_max of 2.00 and 2.50 h. No serious adverse events were reported.

The study showed the pharmacokinetic profiles, as well as good safety and tolerability of 40 mg/20 mg oxycodone/naloxone prolonged-release tablets in Chinese subjects, supporting further development and application in the Chinese population.