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

Yongji He,1,2,* Ling Yang,1,2,* Qianqian Mou,1,2 Xiaotao Cao,1,2 Xiaohong Zhu,1,2 Ying Wang,1,2 Zhu Luo1,2 1Department of Pharmacy, West China Hospital, Sichuan University, Chengdu, People’s Republic of China; 2Clinical Trial Center, National Medical Products Administration Key Laboratory for Clinical Research and Evaluation of Innovative Drugs, West China Hospital, Sichuan University, Chengdu, People’s Republic of China*These authors contributed equally to this workCorrespondence: Zhu Luo, Clinical Trial Center, National Medical Products Administration Key Laboratory for Clinical Research and Evaluation of Innovative Drugs, West China Hospital, Sichuan University, No. 37 Guoxue Lane, Chengdu, Sichuan, 610041, People’s Republic of China, Tel +86 28 85422707, Email [email protected]: The study aimed to assess pharmacokinetics and safety of two oxycodone/naloxone prolonged-release tablet formulations in the Chinese population.Methods: 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.Results: In the fasting study, the mean (± standard deviation, SD) peak concentration (Cmax), area under concentration–time curve from time 0 to the last measurable concentration (AUC0–t) and to infinite time (AUC0–∞), and elimination half-life (t1/2) 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 Cmax (Tmax) were 2.00 h. Parameters of naloxone and its main metabolite naloxone-3β-D-glucuronide were Cmax 89.3 ± 20.6 and 85.6 ± 23.4 ng/mL, AUC0–t 547 ± 104 and 538 ± 131 h*ng/mL, AUC0–∞ 552 ± 104 and 543 ± 133 h*ng/mL, and t1/2 6.59 ± 1.77 and 6.00 ± 1.88 h. Both Tmax were 1.00 h. In the fed study, for oxycodone, parameters were Cmax 71.2 ± 10.2 and 82.3 ± 17.1 ng/mL, AUC0–t 697 ± 171 and 696 ± 154 h*ng/mL, AUC0–∞ 699 ± 173 and 698 ± 155 h*ng/mL, and Tmax 2.50 and 3.50 h. Both t1/2 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 Tmax of 2.00 and 2.50 h. No serious adverse events were reported.Conclusion: 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.Keywords: oxycodone, naloxone, pharmacokinetics, Chinese population