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
Mallinckrodt Inc., 675 James McDonnell Blvd 302-3-W, Hazelwood, MO 63042, USA
- *Corresponding Author:
- Krishna Devarakonda
Mallinckrodt Inc., 675 James McDonnell Blvd 302-3-W
Hazelwood, MO 63042, USA
Tel: (314) 654-3364
Fax: (314) 654-9364
E-mail: [email protected]
Received Date: January 09, 2014; Accepted Date: February 24, 2014; Published Date: March 04, 2014
Citation: Devarakonda K, Morton T, Giuliani M, Kostenbader K, Barrett T (2014) Single-Dose Pharmacokinetics of MNK-795, an Extended-Release Oxycodone and Acetaminophen Combination Analgesic: Results from 2 Active Comparator Studies. J Bioequiv Availab 6: 038-045. doi: 10.4172/jbb.1000178
Copyright: © 2014 Devarakonda K, et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
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.