PMID- 18991473
OWN - NLM
STAT- MEDLINE
DCOM- 20090127
LR  - 20191111
IS  - 1173-2563 (Print)
IS  - 1173-2563 (Linking)
VI  - 28
IP  - 12
DP  - 2008
TI  - Single-dose pharmacokinetics of once-daily cyclobenzaprine extended release 30 mg 
      versus cyclobenzaprine immediate release 10 mg three times daily in healthy young 
      adults : a randomized, open-label, two-period crossover, single-centre study.
PG  - 793-801
LID - 10.2165/0044011-200828120-00007 [doi]
AB  - BACKGROUND AND OBJECTIVE: Cyclobenzaprine immediate release (CIR) has shown 
      efficacy in the treatment of muscle spasm associated with acute, painful 
      musculoskeletal conditions. An extended-release formulation of cyclobenzaprine 
      (CER) has been developed to provide effective muscle spasm relief with once-daily 
      dosing. The objective of this study was to compare the pharmacokinetics of CER 
      and CIR. METHODS: This was a single-centre study of 18 healthy young adults (aged 
      18-45 years). Healthy volunteers were assigned to receive either a single dose of 
      CER 30 mg or three doses of CIR 10 mg on days 1 and 15 (separated by a 14-day 
      washout) in an open-label, two-period crossover study. Pharmacokinetic parameters 
      were monitored through 168 hours after the last dose in each dose period; adverse 
      events (AEs) were monitored during the study through 3 weeks after the last dose 
      of study drug. Cyclobenzaprine was administered as a single oral 30 mg dose of 
      CER or three 10 mg oral doses of CIR given every 8 hours over 24 hours. 
      Statistical tests were conducted against a two-sided alternative hypothesis at a 
      0.05 level of significance with equivalence limits of 80% and 125%. Measures 
      included area under the plasma cyclobenzaprine concentration versus time curve 
      (AUC) to 168 hours and infinity, maximum plasma cyclobenzaprine concentration 
      (C(max)), and time to observed C(max) (t(max)). RESULTS: Eighteen subjects were 
      randomized and 17 completed both periods of the study. CER exhibited a consistent 
      concentration-time profile with a single peak, in contrast to the pharmacokinetic 
      profile for CIR, which displayed multiple peaks and troughs over the 24-hour 
      period. The pharmacokinetic profile of CER 30 mg was characterized by an 
      absorption phase with a median t(max) of approximately 6 hours, compared with the 
      initial peak of CIR (following the first dose) of about 4 hours. Mean plasma 
      concentrations at 4 hours were comparable (12.1 ng/mL for CER; 12.4 ng/mL for 
      CIR). Systemic cyclobenzaprine exposure (AUC and C(max)) was similar across both 
      formulations. The C(max) for CER 30 mg was 19.2 ng/mL (median t(max) = 6 hours) 
      and for CIR (following the third dose) was 18.1 ng/mL (median t(max) = 12 hours). 
      All AEs were mild in intensity; the most common AE was somnolence. CONCLUSION: 
      The pharmacokinetic profile of once-daily CER reflected the mode of 
      administration, providing a controlled release of cyclobenzaprine with sustained 
      plasma concentrations, in contrast to the fluctuating profile of CIR. CER 30 mg 
      once daily and CIR 10 mg three times daily resulted in comparable systemic 
      exposures.
FAU - Darwish, Mona
AU  - Darwish M
AD  - Cephalon, Inc., Frazer, Pennsylvania 19355, USA. mdarwish@cephalon.com
FAU - Hellriegel, Edward T
AU  - Hellriegel ET
FAU - Xie, Fang
AU  - Xie F
LA  - eng
PT  - Comparative Study
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 (Delayed-Action Preparations)
RN  - 0 (Muscle Relaxants, Central)
RN  - 1806D8D52K (Amitriptyline)
RN  - 69O5WQQ5TI (cyclobenzaprine)
SB  - IM
MH  - Adult
MH  - Amitriptyline/administration & dosage/adverse effects/*analogs & 
      derivatives/pharmacokinetics
MH  - Cross-Over Studies
MH  - Delayed-Action Preparations
MH  - Drug Administration Schedule
MH  - Female
MH  - Humans
MH  - Male
MH  - Muscle Relaxants, Central/*pharmacokinetics
EDAT- 2008/11/11 09:00
MHDA- 2009/01/28 09:00
CRDT- 2008/11/11 09:00
PHST- 2008/11/11 09:00 [pubmed]
PHST- 2009/01/28 09:00 [medline]
PHST- 2008/11/11 09:00 [entrez]
AID - 28127 [pii]
AID - 10.2165/0044011-200828120-00007 [doi]
PST - ppublish
SO  - Clin Drug Investig. 2008;28(12):793-801. doi: 10.2165/0044011-200828120-00007.