Background and objective: Food can alter the bioavailability of the controlled-release formulations of many different drugs. This study assessed the effect of food on the pharmacokinetics of once-daily cyclobenzaprine extended-release (CER) in healthy adult subjects.
Methods: Healthy adult volunteers were randomized in an open-label, two-period crossover design to receive a single dose of CER 30 mg on days 1 and 15 (separated by a 14-day drug washout) in either the fed or the fasted state. Pharmacokinetic measures included area under the plasma cyclobenzaprine concentration versus time curve to 168 hours (AUC168) and infinity (AUC∞), maximum plasma cyclobenzaprine concentration (Cmax), time to observed Cmax (tmax), terminal elimination half-life (t1/2β), and absorption lag time (tlag). A food effect, as determined from the Cmax and the AUC, was established if the 90% confidence interval (CI) for the ratio of the mean fed/fasted values fell outside the range of 0.80 to 1.25. Adverse events were monitored throughout the study.
Results: Sixteen healthy volunteers were enrolled (eight men, eight women; mean age 29.7 years), and 15 completed the study. No appreciable differences in the shape of the mean plasma cyclobenzaprine concentration versus time profile, tlag (2 hours) or tmax (fed: 8 hours; fasted: 6 hours) were noted for CER 30 mg in the fed and fasted states. The least-squares mean ratio of fed to fasted state was 1.21 for AUC168 (90% CI 1.11, 1.32), 1.20 for AUC∞ (90% CI 1.11, 1.31), and 1.36 for Cmax (90% CI 1.17, 1.57), which suggested a food effect. Most adverse events were mild in intensity and were comparable in the fed and fasted states.
Conclusion: The results of this study show that an increase in systemic exposure is observed when CER 30 mg is taken with food. CER 30 mg was generally well tolerated, with comparable adverse events in both the fed and the fasted states. The increase in exposure did not appear to impact the tolerability of the formulation.
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van Tulder MW, Touray T, Furlan AD, et al. Muscle relaxants for non-specific low back pain. Cochrane Database Syst Rev 2003; 4(2): CD004252
Chou R, Peterson K, Helfand M. Comparative efficacy and safety of skeletal muscle relaxants for spasticity and musculoskeletal conditions: a systematic review. J Pain Symptom Manage 2004 Aug; 28(2): 140–75
Cyclobenzaprine hydrochloride tablets [package insert]. Corona (CA): Watson Laboratories, Inc., 2006
Darwish M, Hellriegel ET, Xie F. Single-dose pharmaco-kinetics 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. Clin Drug Invest 2008; 28(12): 793–801
Weil A, Narayana A, Chang SCK, et al. Efficacy of cyclo-benzaprine hydrochloride extended-release 15 mg and 30 mg once-daily for low back and neck pain associated with muscle spasms: a pooled analysis of two randomized, double-blind, parallel-group, placebo-controlled, multicenter studies [abstract no. 206]. Pain Med 2008; 9(1): 134–5
Weil AJ, Altman C, Chang SCK, et al. Efficacy of cyclo-benzaprine hydrochloride extended-release 15 and 30 mg once daily for low back and neck pain associated with muscle spasm: a pooled analysis of two randomized, double-blind, parallel-group, placebo-controlled, multicenter studies [poster no. 206]. 24th Annual Meeting of the American Academy of Pain Medicine; 2008 Feb 12–16; Orlando (FL)
Cramer MP, Saks SR. Translating safety, efficacy and compliance into economic value for controlled release dosage forms. Pharmacoeconomics 1994 Jun; 5(6): 482–504
Soma [package insert]. Somerset (NJ): MedPointe Pharmaceuticals, 2007
Peterson GM, McLean S, Millingen KS. Food does not affect the bioavailability of baclofen. Med J Aust 1985 Jun 24; 142(13): 689–90
Shah J, Wesnes KA, Kovelesky RA, et al. Effects of food on the single-dose pharmacokinetics/pharmacodynamics of tizanidine capsules and tablets in healthy volunteers. Clin Ther 2006 Sep; 28(9): 1308–17
Locniskar A, Greenblatt DJ, Zinny MA, et al. Absolute bioavailability and effect of food and antacid on diazepam absorption from a slow-release preparation. J Clin Pharmacol 1984 May; 24(5–6): 255–63
Chandra R, Liu P, Breen JD, et al. Clinical pharmaco-kinetics and gastrointestinal tolerability of a novel extended-release microsphere formulation of azithromycin. Clin Pharmacokinet 2007; 46(3): 247–59
Wagstaff AJ, Figgitt DP. Extended-release metformin hydrochloride: single-composition osmotic tablet formulation. Treat Endocrinol 2004; 3(5): 327–32
Guay DR. Clinical pharmacokinetics of drugs used to treat urge incontinence. Clin Pharmacokinet 2003; 42(14): 1243–85
Auiler JF, Liu K, Lynch JM, et al. Effect of food on early drug exposure from extended-release stimulants: results from the Concerta, Adderall XR Food Evaluation (CAFE) study. Curr Med Res Opin 2002; 18(5): 311–6
Wilder BJ, Leppik I, Hietpas TJ, et al. Effect of food on absorption of Dilantin Kapseals and Mylan extended phenytoin sodium capsules. Neurology 2001 Aug 28; 57(4): 582–9
World Medical Association. Declaration of Helsinki: ethical principles for medical research involving human subjects [online]. Available from http://http://www.wma.net/e/policy/pdf/17c.pdf [Accessed 2008 Oct 10]
ECR Pharmaceuticals (Richmond, VA, USA) sponsored this study. Cephalon, Inc. (Frazer, PA, USA) acquired the North American rights to cyclobenzaprine extended-release (Amrix®) in August 2007. Editorial support for the preparation of this manuscript was provided by Peloton Advantage, LLC; funding was provided by Cephalon, Inc. The authors are employees of Cephalon, Inc., Frazer, PA, USA. The authors acknowledge the contributions of Islah Ahmed, MD (former Medical Director and Study Monitor, Omnicare Clinical Research, Inc., Troy, NY, USA), and the medical review by Charles Altman, MD, MBA (Cephalon, Inc., Frazer, PA, USA).
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Darwish, M., Xie, F. Effect of Food on the Pharmacokinetics of Once-Daily Cyclobenzaprine Extended-Release 30 mg. Clin. Drug Investig. 29, 145–152 (2009). https://doi.org/10.2165/00044011-200929030-00001