title: Comparison of single-dose and multiple-dose pharmacokinetics between two formulations of hydrocodone bitartrate/acetaminophen: immediate-release versus biphasic immediate-release/extended release.
abstract: OBJECTIVE
  This study aimed to compare the single-dose and steady-state pharmacokinetics (PK) of biphasic immediate-release (IR)/extended-release (ER) hydrocodone bitartrate (HB)/acetaminophen (APAP) and IR HB/APAP.
  
  
  METHODS
  The study was conducted in a contract research center.
  
  
  METHODS
  The study included healthy adults.
  
  
  METHODS
  In a three-way crossover study, Study 1, participants received the following treatments: (A1) a single dose of IR/ER HB/APAP 7.5/325 mg one tablet, followed by one tablet every 12 hours (q12h); (B1) a single dose of IR/ER HB/APAP 7.5/325 mg two tablets, followed by two tablets q12h; (C1) a single dose of IR HB/APAP 7.5/325 mg two tablets (one tablet at hours 0 and 6), followed by one tablet q6h. In a two-way crossover study, Study 2, participants received the following treatments: (A2) an initial dose of IR/ER HB/APAP 7.5/325 mg three tablets, followed by two tablets q12h; (B2) three doses of IR HB/APAP 7.5/325 mg one tablet q4h, followed by one tablet q6h.
  
  
  METHODS
  PK values were compared, and adverse events were assessed.
  
  
  RESULTS
  Single-dose and steady-state area under the concentration-time curves for hydrocodone and APAP were similar for IR/ER and IR HB/APAP; the steady-state peak plasma concentrations (C max) at steady state were also similar, but single-dose C max for hydrocodone was lower for IR/ER HB/APAP. For most PK parameters, 90% confidence intervals for geometric least squares mean ratios were not meaningfully different (80%-125%). Steady state was achieved in 2-3 days for IR/ER HB/APAP and in 2 days for IR HB/APAP. Median time to C max was longer for IR/ER HB/APAP versus IR HB/APAP (P,0.05). Adverse events were similar across treatments.
  
  
  CONCLUSIONS
  PK outcomes and tolerability were similar for IR/ER HB/APAP and IR HB/APAP.
authors.affiliation: Department of Clinical Pharmacology, Mallinckrodt Pharmaceuticals, Hazelwood, MO, USA.
authors.forename: Krishna
authors.initials: K
authors.lastname: Devarakonda
authors.affiliation: Independent Pharmaceuticals Professional, Mallinckrodt Pharmaceuticals, Hazelwood, MO, USA.
authors.forename: Kenneth
authors.initials: K
authors.lastname: Kostenbader
authors.affiliation: Research and Development, Mallinckrodt Pharmaceuticals, Hazelwood, MO, USA.
authors.forename: Michael J
authors.initials: MJ
authors.lastname: Giuliani
authors.affiliation: Clinical Affairs and Program Management, Mallinckrodt Pharmaceuticals, Hazelwood, MO, USA.
authors.forename: Jim L
authors.initials: JL
authors.lastname: Young
keywords: acute pain; extended release; fixed-dose combination; hydrocodone; opioid analgesic; pharmacokinetics