PMID- 25813216
OWN - NLM
STAT- MEDLINE
DCOM- 20160704
LR  - 20181202
IS  - 1179-1918 (Electronic)
IS  - 1173-2563 (Linking)
VI  - 35
IP  - 5
DP  - 2015 May
TI  - Dose proportionality of a hydrocodone extended-release tablet formulated with 
      abuse-deterrence technology.
PG  - 291-7
LID - 10.1007/s40261-015-0280-z [doi]
AB  - BACKGROUND AND OBJECTIVE: This open-label, crossover study evaluated the dose 
      proportionality of a hydrocodone extended-release (ER) tablet employing the 
      CIMA((R)) 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 (AUCinfinity). Dose proportionality 
      was concluded if the confidence interval (CI) of the slope of the regression line 
      for C max and AUCinfinity 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 AUCinfinity was 199, 382, 592, 766, and 1189 
      ng.h/mL for hydrocodone ER 15, 30, 45, 60, and 90 mg, respectively. C max and 
      AUCinfinity increased linearly with increasing dose. The 90 % CIs of the slope of the 
      regression line for C max (0.880-0.922) and AUCinfinity (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. CONCLUSION: Hydrocodone exposure increased in a 
      dose-proportional manner after administration of hydrocodone ER 15-90 mg tablets 
      in healthy, naltrexone-blocked subjects.
FAU - Darwish, Mona
AU  - Darwish M
AD  - Teva Pharmaceuticals, 41 Moores Road, PO Box 4011, Frazer, PA, 19355, USA.
FAU - Yang, Ronghua
AU  - Yang R
FAU - Tracewell, William
AU  - Tracewell W
FAU - Robertson, Philmore Jr
AU  - Robertson P Jr
FAU - Bond, Mary
AU  - Bond M
LA  - eng
PT  - Clinical Trial, Phase I
PT  - Journal Article
PT  - Randomized Controlled Trial
PT  - Research Support, Non-U.S. Gov't
PL  - New Zealand
TA  - Clin Drug Investig
JT  - Clinical drug investigation
JID - 9504817
RN  - 0 (Analgesics, Opioid)
RN  - 0 (Delayed-Action Preparations)
RN  - 6YKS4Y3WQ7 (Hydrocodone)
SB  - IM
MH  - Adolescent
MH  - Adult
MH  - Analgesics, Opioid/*administration & dosage/blood/*pharmacokinetics
MH  - Area Under Curve
MH  - Cross-Over Studies
MH  - Delayed-Action Preparations/*administration & dosage
MH  - Dose-Response Relationship, Drug
MH  - Female
MH  - Healthy Volunteers
MH  - Humans
MH  - Hydrocodone/*administration & dosage/blood/*pharmacokinetics
MH  - Male
MH  - Middle Aged
MH  - Young Adult
EDAT- 2015/03/31 06:00
MHDA- 2016/07/05 06:00
CRDT- 2015/03/28 06:00
PHST- 2015/03/28 06:00 [entrez]
PHST- 2015/03/31 06:00 [pubmed]
PHST- 2016/07/05 06:00 [medline]
AID - 10.1007/s40261-015-0280-z [doi]
PST - ppublish
SO  - Clin Drug Investig. 2015 May;35(5):291-7. doi: 10.1007/s40261-015-0280-z.