生物学的同等性とバイオアベイラビリティのジャーナル

概要

Single-Dose Pharmacokinetics of MNK-795, an Extended-Release Oxycodone and Acetaminophen Combination Analgesic: Results from 2 Active Comparator Studies

Krishna Devarakonda, Terri Morton, Michael Giuliani, Kenneth Kostenbader and Thomas Barrett

MNK-795, a combination oxycodone (OC) and acetaminophen (APAP) analgesic (OC/APAP ER), is a bilayer product with immediate-release (IR) and extended-release (ER) properties. Two single-center, open-label, randomized, phase 1, crossover studies were conducted in healthy participants (N=48 for each trial) to characterize the pharmacokinetics (PK) and bioavailability of OC/APAP ER. Study 1 compared the single-dose PK and bioavailability following administration of 1 or 2 tablets of OC/APAP ER with an IR OC/APAP formulation. Study 2 assessed the single-dose PK and bioavailability of 2 tablets of OC/APAP ER compared with those of marketed forms of IR oxycodone, IR tramadol/APAP, and IR OC/APAP. Safety and tolerability were monitored. In both studies, OC/ APAP ER demonstrated a bimodal OC release pattern, with a rapid rise and no lag in plasma concentrations after dosing, followed by an ER period with concentrations peaking 3 to 4 hours postdose and extending over 12 hours. Acetaminophen concentrations also demonstrated an initial rapid rise but tapered off at 7 to 12 hours postdose. Bioavailability and overall exposure of oxycodone and acetaminophen were comparable between single doses of OC/APAP ER and IR comparators (2 doses, 6 hours apart). Adverse events were consistent with those seen with opioids.