Single-Dose Pharmacokinetics of Once-Daily Cyclobenzaprine Extended Release 30 mg versus Cyclobenzaprine Immediate Release 10 mg Three Times Daily in Healthy Young Adults

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.