title: Pharmacokinetics and bioavailability of oxycodone and acetaminophen following single-dose administration of MNK-795, a dual-layer biphasic IR/ER combination formulation, under fed and fasted conditions.
abstract: BACKGROUND
  XARTEMIS™ XR (formerly MNK-795) is a combination oxycodone (OC) and acetaminophen (APAP) analgesic with both immediate-release and extended-release (ER) components (ER OC/APAP). The tablets are designed with gastric-retentive ER oral delivery technology that releases the ER component at a controlled rate in the upper gastrointestinal tract. Because consumption of food has demonstrated an impact on the pharmacokinetics (PK) of some marketed products using gastric-retentive ER oral delivery technology, a characterization of the effects of fed (high- and low-fat diets) versus fasted conditions on the PK of ER OC/APAP was performed.
  
  
  METHODS
  This Phase I study used an open-label randomized single-dose three-period six-sequence crossover single-center design. Healthy adult participants (n=48) were randomized to receive two tablets of ER OC/APAP under three conditions: following a high-fat meal; following a low-fat meal; and fasted. Plasma concentration versus time data from predose throughout designated times up to 48 hours postdose was used to estimate the PK parameters of oxycodone and APAP.
  
  
  RESULTS
  Thirty-one participants completed all three treatment periods. Both oxycodone and APAP were rapidly absorbed under fasted conditions. Total oxycodone and APAP exposures (area under the plasma drug concentration-time curve [AUC]) from ER OC/APAP were not significantly affected by food, and minimal changes to maximum observed plasma concentration for oxycodone and APAP were also noted. However, food marginally delayed the time to maximum observed plasma concentration of oxycodone and APAP. There was no indication that tolerability was affected by food.
  
  
  CONCLUSIONS
  The findings from this study suggest that ER OC/APAP can be administered with or without food.
authors.affiliation: Clinical Pharmacology and Pharmacokinetics, Hazelwood, MO, USA.
authors.forename: Krishna
authors.initials: K
authors.lastname: Devarakonda
authors.affiliation: Clinical Pharmacology and Pharmacokinetics, Hazelwood, MO, USA.
authors.forename: Terri
authors.initials: T
authors.lastname: Morton
authors.affiliation: Clinical Operations, Hazelwood, MO, USA.
authors.forename: Rachel
authors.initials: R
authors.lastname: Margulis
authors.affiliation: Research and Development, Hazelwood, MO, USA.
authors.forename: Michael
authors.initials: M
authors.lastname: Giuliani
authors.affiliation: Clinical Affairs, Mallinckrodt Inc., Hazelwood, MO, USA.
authors.forename: Thomas
authors.initials: T
authors.lastname: Barrett
mesh_terms: D000082:Acetaminophen / Q000008:administration & dosage / Q000493:pharmacokinetics*; D000284:Administration, Oral; D000293:Adolescent; D000328:Adult; D000700:Analgesics / Q000008:administration & dosage / Q000493:pharmacokinetics; D000701:Analgesics, Opioid / Q000008:administration & dosage / Q000493:pharmacokinetics*; D019540:Area Under Curve; D001682:Biological Availability; D018592:Cross-Over Studies; D003692:Delayed-Action Preparations; D004041:Dietary Fats / Q000008:administration & dosage; D004338:Drug Combinations; D005215:Fasting; D005260:Female; D018565:Food-Drug Interactions; D006801:Humans; D008297:Male; D008875:Middle Aged; D010098:Oxycodone / Q000008:administration & dosage / Q000493:pharmacokinetics*; D013607:Tablets; D055815:Young Adult
chemical_list: D000700:Analgesics; D000701:Analgesics, Opioid; D003692:Delayed-Action Preparations; D004041:Dietary Fats; D004338:Drug Combinations; D013607:Tablets; C514822:oxycodone-acetaminophen; D000082:Acetaminophen; D010098:Oxycodone
keywords: acute pain; extended release; fed conditions; opioid fixed dose combination