title: A pharmacokinetic evaluation of single and multiple doses of extended-release hydrocodone bitartrate in subjects experiencing surgical or osteoarthritic pain.
abstract: OBJECTIVE
  To assess the single-dose and steady-state pharmacokinetics of a single-entity hydrocodone extended-release (ER) formulation in patients enrolled in two separate phase 2 clinical studies.
  
  
  METHODS
  Both studies were multicenter clinical studies.
  
  
  METHODS
  In study 1, 115 subjects with postsurgical pain (bunionectomy) received single doses of 10, 20, 30, or 40 mg hydrocodone-ER, 10 mg hydrocodone/325 mg acetaminophen immediate-release (IR), or placebo. In study 2, 37 subjects with osteoarthritic pain received doses of 10, 20, 30, or 40 mg of hydrocodone- ER twice-daily for 7 days. Venous blood samples were taken periodically up to 24 hours postdosing after the single dose (study 1) or after 7 days of dosing (study 2) and were assayed for concentrations of hydrocodone and its major metabolites.
  
  
  METHODS
  Standard pharmacokinetic parameters were estimated by noncompartmental analysis methods.
  
  
  RESULTS
  Following a single dose of hydrocodone-ER, Tmax was prolonged to approximately 6 hours at all dose levels of hydrocodone-ER compared with 2.9 hours for the IR formulation. All doses of hydrocodone-ER formulations provided prolonged and sustained release of hydrocodone throughout the 12-hour dosing interval with reduced peak-to-trough fluctuation at steady state compared with hydrocodone/acetaminophen-IR comparator. Both single-dose and steadystate mean Cmax and AUClast values showed reasonable dose-proportionality. Norhydrocodone and hydromorphone plasma concentrations were 32-38 percent and <2.1 percent, respectively, of hydrocodone concentrations in both studies.
  
  
  CONCLUSIONS
  The sustained plasma concentrations of hydrocodone support twice-daily dosing with a 12-hour dosing interval.
authors.affiliation: Senior Scientific Advisor, Clinical Development, Zogenix, Inc., San Diego, California.
authors.forename: Cynthia Y
authors.initials: CY
authors.lastname: Robinson
authors.affiliation: Vice President, Pharmacometrics, Institute for Clinical Pharmacodynamics, Latham, New York; Adjunct Assistant Research Professor, School of Pharmacy and Pharmaceutical Sciences, SUNY University at Buffalo, Buffalo, New York.
authors.forename: Christopher M
authors.initials: CM
authors.lastname: Rubino
authors.affiliation: President, Zogenix, Inc., Emeryville, California.
authors.forename: Stephen J
authors.initials: SJ
authors.lastname: Farr
mesh_terms: D000328:Adult; D000701:Analgesics, Opioid / Q000008:administration & dosage / Q000493:pharmacokinetics; D018771:Arthralgia / Q000188:drug therapy* / Q000209:etiology / Q000378:metabolism; D018592:Cross-Over Studies; D003692:Delayed-Action Preparations; D004305:Dose-Response Relationship, Drug; D004334:Drug Administration Schedule; D005260:Female; D006801:Humans; D006853:Hydrocodone / Q000008:administration & dosage / Q000493:pharmacokinetics*; D008297:Male; D008875:Middle Aged; D010003:Osteoarthritis / Q000150:complications* / Q000188:drug therapy / Q000378:metabolism; D010147:Pain Measurement; D016896:Treatment Outcome
chemical_list: D000701:Analgesics, Opioid; D003692:Delayed-Action Preparations; D006853:Hydrocodone