title: Pharmacokinetic Profile and Sustained 24-hour Analgesia of a Once-daily Hydrocodone Bitartrate Extended-release Tablet with Abuse-deterrent Properties.
abstract: OBJECTIVE
  The purpose of this study was to evaluate the pharmacokinetics (PK) and 24-hour analgesic effectiveness of once-daily, single-entity, extended-release hydrocodone (HYD) with abuse-deterrent properties.
  
  
  METHODS
  Four studies were included. Three open-label PK studies had the following designs: single-dose, 5-treatment, 4-period, crossover, dose-proportionality study; HYD 120 mg for 5 days (steady-state study 1); 2-treatment, 2-period, multiple-dose crossover study assessing the relative bioavailability of HYD 30 mg and hydrocodone 7.5 mg/ibuprofen 200 mg administered every 6 hours (steady-state study 2). A long-term, open-label study assessed the safety and effectiveness of HYD 20 to 120 mg in patients during a 52-week maintenance period.
  
  
  RESULTS
  Thirty-one, 25, and 22 healthy subjects completed the dose-proportionality study, steady-state study 1, and steady-state study 2, respectively, while 410 patients with moderate to severe chronic nonmalignant and non-neuropathic pain completed the long-term effectiveness study. Mean systemic exposure and peak plasma concentration were dose proportional after administration of single doses of HYD 20 to 120 mg. Pharmacokinetic profiles were comparable at day 1 and day 5 after administration of HYD 120 mg once daily. Once-daily HYD 30 mg was associated with lower-fluctuating plasma hydrocodone concentrations compared with immediate-release hydrocodone 7.5 mg/ibuprofen 200 mg administered every 6 hours. In the long-term study, pain control was consistent over the 24-hour dosing interval.
  
  
  CONCLUSIONS
  Once-daily HYD exhibits linear, dose-proportional PK properties and is associated with a lower variability in plasma hydrocodone concentrations when compared with an immediate-release hydrocodone combination product. Notably, analgesia provided by HYD is sustained during the 24-hour dosing interval. ClinicalTrials.gov identifier: NCT01400139 (Study 4).
authors.affiliation: Purdue Pharma LP, Stamford, Connecticut. Electronic address: Ram.Kapil@pharma.com.
authors.forename: Ram P
authors.initials: RP
authors.lastname: Kapil
authors.affiliation: Purdue Pharma LP, Stamford, Connecticut.
authors.forename: Alessandra
authors.initials: A
authors.lastname: Cipriano
authors.affiliation: Purdue Pharma LP, Stamford, Connecticut.
authors.forename: Warren
authors.initials: W
authors.lastname: Wen
authors.affiliation: Purdue Pharma LP, Stamford, Connecticut.
authors.forename: Shau
authors.initials: S
authors.lastname: Yu Lynch
authors.affiliation: Purdue Pharma LP, Stamford, Connecticut.
authors.forename: Ellie
authors.initials: E
authors.lastname: He
authors.affiliation: Purdue Pharma LP, Stamford, Connecticut.
authors.forename: Salvatore V
authors.initials: SV
authors.lastname: Colucci
authors.affiliation: Purdue Pharma LP, Stamford, Connecticut.
authors.forename: Stephen C
authors.initials: SC
authors.lastname: Harris
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000698:Analgesia / Q000379:methods; D059350:Chronic Pain / Q000188:drug therapy*; D018592:Cross-Over Studies; D003692:Delayed-Action Preparations; D004334:Drug Administration Schedule; D005260:Female; D006801:Humans; D006853:Hydrocodone / Q000008:administration & dosage / Q000493:pharmacokinetics*; D008137:Longitudinal Studies; D008297:Male; D008875:Middle Aged; D019966:Substance-Related Disorders / Q000517:prevention & control*; D013607:Tablets; D055815:Young Adult
chemical_list: D003692:Delayed-Action Preparations; D013607:Tablets; D006853:Hydrocodone
keywords: analgesia; effectiveness; hydrocodone; pharmacokinetics