+ Site Statistics
References:
54,258,434
Abstracts:
29,560,870
PMIDs:
28,072,757
+ Search Articles
+ PDF Full Text Service
How our service works
Request PDF Full Text
+ Follow Us
Follow on Facebook
Follow on Twitter
Follow on LinkedIn
+ Subscribe to Site Feeds
Most Shared
PDF Full Text
+ Translate
+ Recently Requested

Comparison of the single-dose pharmacokinetics of once-daily cyclobenzaprine extended-release 30 mg and cyclobenzaprine immediate-release 10 mg three times daily in the elderly: a randomized, open-label, crossover study



Comparison of the single-dose pharmacokinetics of once-daily cyclobenzaprine extended-release 30 mg and cyclobenzaprine immediate-release 10 mg three times daily in the elderly: a randomized, open-label, crossover study



Drugs and Aging 26(2): 95-101



The clinical utility of cyclobenzaprine for the treatment of muscle spasm associated with acute, painful musculoskeletal conditions is limited by cholinergic adverse effects associated with its use. As expected, these effects may be pronounced in the elderly in whom altered renal and hepatic function may change drug pharmacokinetics. The goal of this study was to characterize the pharmacokinetics of the extended-release formulation of cyclobenzaprine (CER) in elderly volunteers. This randomized, open-label, two-period crossover study compared the pharmacokinetics, safety and tolerability of a single oral 30-mg dose of CER with those of 10 mg of cyclobenzaprine immediate-release (CIR) administered every 8 hours for a total of three doses in 18 healthy volunteers aged 65-75 years. Volunteers were assigned to either CER or CIR on days 1 and 15 (separated by a 14-day washout). Outcome measures included area under the plasma cyclobenzaprine concentration versus time curve (AUC) to 168 hours (AUC168) and infinity (AUC infinity), peak plasma cyclobenzaprine concentration (Cmax), time to observed Cmax (tmax) and terminal elimination half-life of cyclobenzaprine. Adverse events (AEs) were monitored during the study through 3 weeks after the last dose of study drug. Eighteen subjects were randomized and completed the first treatment period; 17 completed both periods of the study. The pharmacokinetics of CER 30 mg were characterized by an absorption phase with a median t(max) of 8 hours compared with an initial peak for CIR (following the first dose) at about 5 hours. Plasma cyclobenzaprine concentrations at 5 hours were 13.6 ng/mL for CER and 11.0 ng/mL for CIR. Systemic cyclobenzaprine exposure (AUC168, AUC infinity and Cmax) was similar for a single dose of CER and three doses of CIR and met bioequivalence criteria. Most AEs were mild in intensity; the most common AE was somnolence. No serious AEs or discontinuations as a result of AEs were reported during the study. Once-daily CER 30 mg exhibited controlled release of cyclobenzaprine and resulted in systemic exposure similar to that of CIR in subjects aged 65-75 years.

Please choose payment method:






(PDF emailed within 1 workday: $29.90)

Accession: 052247980

Download citation: RISBibTeXText

PMID: 19220066


Related references

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. Clinical Drug Investigation 28(12): 793-801, 2008

Comparison of the Single-Dose Pharmacokinetics of Once-Daily Cyclobenzaprine Extended-Release 30 mg and Cyclobenzaprine Immediate-Release 10 mg Three Times Daily in the Elderly. Drugs & Aging 26(2): 95-101, 2009

Effect of food on the pharmacokinetics of once-daily cyclobenzaprine extended-release 30 mg: a randomized, open-label, crossover, single-centre study. Clinical Drug Investigation 29(3): 145-152, 2009

A pharmacokinetic comparison of single doses of once-daily cyclobenzaprine extended-release 15 mg and 30 mg: a randomized, double-blind, two-period crossover study in healthy volunteers. Clinical Therapeutics 31(1): 108-114, 2009

Steady-state pharmacokinetics of once-daily cyclobenzaprine extended release: a randomized, double-blind, 2-period crossover study in healthy volunteers. Clinical Therapeutics 33(6): 746-753, 2011

Pharmacokinetics of gabapentin after a single day and at steady state following the administration of gastric-retentive- extended-release and immediate-release tablets: a randomized, open-label, multiple-dose, three-way crossover, exploratory study in healthy subjects. Clinical Therapeutics 30(5): 909-916, 2008

Pharmacokinetics of a new once-daily controlled-release formulation of aceclofenac in Korean healthy subjects compared with immediate-release aceclofenac and the effect of food: a randomized, open-label, three-period, crossover, single-centre study. Clinical Drug Investigation 32(2): 111-119, 2012

Pharmacokinetic profile of once-daily cyclobenzaprine extended-release. Expert Opinion on Drug Metabolism and Toxicology 6(11): 1425-1436, 2011

Pharmacokinetics of a fixed-dose combination of atorvastatin and metformin extended release versus concurrent administration of individual formulations: a randomized, open-label, two-treatment, two-period, two-sequence, single-dose, crossover, bioequivalence study. Clinical Drug Investigation 31(12): 853-863, 2012

Single-dose pharmacokinetics of 2 or 3 tablets of biphasic immediate-release/extended-release hydrocodone bitartrate/acetaminophen (MNK-155) under fed and fasted conditions: two randomized open-label trials. Bmc Pharmacology and Toxicology 16: 31, 2016

Once-daily, prolonged-release tacrolimus vs twice-daily, immediate-release tacrolimus in de novo living-donor liver transplantation: A Phase 4, randomized, open-label, comparative, single-center study. Clinical Transplantation 32(9): E13376, 2018

Dose proportionality and pharmacokinetics of extended-release (OROS®) hydromorphone: a phase 1, open-label, randomized, crossover study in healthy Taiwanese subjects. International Journal of Clinical Pharmacology and Therapeutics 52(3): 217-226, 2014

P4-403: Extended-release (Er) memantine capsule (28 mg, once daily): A multiple-dose, open-label study evaluating steady-state pharmacokinetics in healthy volunteers. Alzheimer's & Dementia 4(4): T792-T793, 2008

A phase I, randomized, open-label, crossover study of the single-dose pharmacokinetic properties of guanfacine extended-release 1-, 2-, and 4-mg tablets in healthy adults. Clinical Therapeutics 29(4): 617-625, 2007

Comparative pharmacokinetics of a once-daily tramadol extended-release tablet and an immediate-release reference product following single-dose and multiple-dose administration. Journal of Clinical Pharmacology 50(5): 544-553, 2010