Oxycodone hydrochloride

Oxycodone hydrochloride, a water soluble drug, was obtained from Daiichi Sankyo Propharma Co., Ltd. (Japan). Hydroxypropylcellulose (HPC-H; fine particle grade, 1000 mPas to 4000 mPas, HPC-SL; 150 mPas to 400 mPas) was purchased from Nippon Soda Co., Ltd. (Japan). Hypromellose acetate succinate (Shin-Etsu AQOAT; LF) was purchased from Shin-Etsu Chemical Co., Ltd. (Japan). D-Mannitol was purchased from Merck Millipore Corporation (Germany). Magnesium stearate (Hyqual, vegetable source) was purchased from Mallinckrodt Pharmaceuticals (USA). All other chemicals and solvents were of reagent grade. The reference product, OxyContin, was purchased from Japanese market purchasing (Shionogi & Co., Ltd., Japan).

The agents used in this study were morphine hydrochloride hydrate (Daiichi Sankyo), oxycodone hydrochloride (Daiichi Sankyo), naloxone (Daiichi Sankyo), and β‐funaltrexamine (Axon Medchem). Morphine was diluted in saline to 10, 30, 60 and 100 mg/kg doses and oxycodone was diluted in saline to a 66 mg/kg dose. We chose an oral oxycodone dose of 66 mg/kg because the ratio of the antinociceptive titer of morphine and oxycodone is 3:2 for its oral administration in humans.¹⁰ A stainless steel tube was inserted through the esophagus to the stomach, through which 2 mL of morphine, oxycodone or saline solution was administered. Naloxone and β‐FNA were dissolved in saline solution. Naloxone (1 mg/kg) was injected intraperitoneally (IP) 10 min prior to morphine, whereas β‐FNA (20 mg/kg) was injected subcutaneously 24 h prior to morphine.
General status, such as sedative condition and motility, was carefully observed after drug administration.