title: Dose proportionality of a hydrocodone extended-release tablet formulated with abuse-deterrence technology.
abstract: OBJECTIVE
  This open-label, crossover study evaluated the dose proportionality of a hydrocodone extended-release (ER) tablet employing the CIMA(®) Abuse-Deterrence Technology platform.
  
  
  METHODS
  Healthy volunteers were randomized to receive single doses of hydrocodone ER 15, 30, 45, 60, and 90 mg separated by a minimum 14-day washout. Subjects received naltrexone to minimize opioid-related adverse events (AEs). Blood samples were collected for 72 h after each hydrocodone administration. Pharmacokinetic measures included maximum observed plasma hydrocodone concentration (C max) and area under the plasma concentration-time curve from time zero to infinity (AUC∞). Dose proportionality was concluded if the confidence interval (CI) of the slope of the regression line for C max and AUC∞ versus dose fell within 0.875-1.125.
  
  
  RESULTS
  In total, 60 subjects were evaluable for pharmacokinetics. The mean C max was 12.6, 20.7, 30.3, 41.2, and 62.5 ng/mL and the mean AUC∞ was 199, 382, 592, 766, and 1189 ng.h/mL for hydrocodone ER 15, 30, 45, 60, and 90 mg, respectively. C max and AUC∞ increased linearly with increasing dose. The 90 % CIs of the slope of the regression line for C max (0.880-0.922) and AUC∞ (0.984-1.026) indicated systemic exposure to hydrocodone increased in a dose-proportional manner. In these naltrexone-blocked subjects, no increased incidence of AEs was apparent with increasing dose.
  
  
  CONCLUSIONS
  Hydrocodone exposure increased in a dose-proportional manner after administration of hydrocodone ER 15-90 mg tablets in healthy, naltrexone-blocked subjects.
authors: Teva Pharmaceuticals, 41 Moores Road, PO Box 4011, Frazer, PA, 19355, USA.
authors: Mona
authors: M
authors: Darwish
authors: Ronghua
authors: R
authors: Yang
authors: William
authors: W
authors: Tracewell
authors: Philmore
authors: P
authors: Robertson
authors: Mary
authors: M
authors: Bond
mesh_terms: D000293:Adolescent; D000328:Adult; D000701:Analgesics, Opioid / Q000008:administration & dosage* / Q000097:blood / Q000493:pharmacokinetics*; D019540:Area Under Curve; D018592:Cross-Over Studies; D003692:Delayed-Action Preparations / Q000008:administration & dosage*; D004305:Dose-Response Relationship, Drug; D005260:Female; D064368:Healthy Volunteers; D006801:Humans; D006853:Hydrocodone / Q000008:administration & dosage* / Q000097:blood / Q000493:pharmacokinetics*; D008297:Male; D008875:Middle Aged; D055815:Young Adult
chemical_list: D000701:Analgesics, Opioid; D003692:Delayed-Action Preparations; D006853:Hydrocodone