title: Oral Abuse Potential, Pharmacokinetics, and Safety of Once-Daily, Single-Entity, Extended-Release Hydrocodone (HYD) in Recreational Opioid Users.
abstract: OBJECTIVE
  A once-daily, extended-release hydrocodone bitartrate tablet with abuse-deterrent properties (Hysingla ER [HYD]) is available for the treatment of chronic pain in appropriate patients. This study evaluated the oral abuse potential and pharmacokinetics (PK) of HYD intact, chewed, or milled to fine particles in comparison with hydrocodone solution or placebo.
  
  
  METHODS
  Single-center, double-blind, randomized, five-period, five-treatment crossover study.
  
  
  METHODS
  Healthy adult, nondependent, recreational opioid users.
  
  
  METHODS
  Forty subjects received orally administered treatments of hydrocodone 60 mg solution, HYD 60 mg intact, HYD 60 mg chewed, HYD 60 mg milled to fine particles, or placebo, separated by a five- to seven-day washout. Assessments over 36 hours postdose included subjective measures of drug liking and willingness to take drug again (assessed using visual analog scales [VAS]), pupillometry, PK, and safety measures.
  
  
  RESULTS
  Following oral administration, HYD intact, HYD chewed, and HYD fine particles led to significantly lower "at this moment" drug liking compared with hydrocodone solution. HYD intact and chewed were significantly different from hydrocodone solution on overall drug liking, take drug again, and good effects. Pupil constriction, as measured by pupillometry, occurred later with HYD intact and HYD chewed than with hydrocodone solution. Across treatments (hydrocodone solution, HYD fine particles, HYD chewed, and HYD intact, respectively), mean C max and rate of absorption (C max /T max ) values decreased, respectively, and median T max values increased, respectively. Safety was consistent with the known effects of opioid agonists.
  
  
  CONCLUSIONS
  HYD demonstrated reduced oral abuse potential compared with hydrocodone solution in healthy adult, nondependent, recreational opioid users.
authors.affiliation: Clinical Pharmacology, Purdue Pharma L.P., Stamford, Connecticut, USA.
authors.forename: Stephen C
authors.initials: SC
authors.lastname: Harris
authors.affiliation: Clinical Pharmacology, Purdue Pharma L.P., Stamford, Connecticut, USA.
authors.forename: Alessandra
authors.initials: A
authors.lastname: Cipriano
authors.affiliation: Biostatistics and Statistical Programming, Purdue Pharma L.P., Stamford, CT, USA.
authors.forename: Salvatore V
authors.initials: SV
authors.lastname: Colucci
authors.affiliation: Clinical Pharmacology, Purdue Pharma L.P., Stamford, Connecticut, USA.
authors.forename: Ram P
authors.initials: RP
authors.lastname: Kapil
authors.affiliation: Early Phase INC Research, Toronto, Ontario, Canada.
authors.forename: Pierre
authors.initials: P
authors.lastname: Geoffroy
authors.affiliation: Early Phase INC Research, Toronto, Ontario, Canada.
authors.forename: Talar
authors.initials: T
authors.lastname: Hopyan
authors.affiliation: Early Phase INC Research, Toronto, Ontario, Canada.
authors.forename: Naama
authors.initials: N
authors.lastname: Levy-Cooperman
mesh_terms: D000284:Administration, Oral; D000328:Adult; D000701:Analgesics, Opioid / Q000008:administration & dosage* / Q000493:pharmacokinetics*; D018592:Cross-Over Studies; D003692:Delayed-Action Preparations / Q000008:administration & dosage / Q000493:pharmacokinetics; D004311:Double-Blind Method; D004334:Drug Administration Schedule; D004339:Drug Compounding; D005260:Female; D006801:Humans; D006853:Hydrocodone / Q000008:administration & dosage* / Q000493:pharmacokinetics*; D008297:Male; D008409:Mastication / Q000502:physiology; D008875:Middle Aged; D009293:Opioid-Related Disorders / Q000188:drug therapy / Q000378:metabolism*; D055815:Young Adult
chemical_list: D000701:Analgesics, Opioid; D003692:Delayed-Action Preparations; D006853:Hydrocodone
keywords: Abuse Deterrent; Abuse Potential; HYD; Hydrocodone; Pain