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.
OBJECTIVE
The purpose of this study was to compare the pharmacokinetics and tolerability of single oral doses of cyclobenzaprine extended-release (CER) 15- and 30-mg capsules.


METHODS
This was a randomized, double-blind, 2-period crossover study in healthy adults aged 18 to 40 years. Subjects were assigned to receive a single dose of either CER 15 mg or 30 mg on days 1 and 15, separated by a 14-day washout. Study comparisons included the plasma cyclobenzaprine AUC to 168 hours after dosing (AUC(0-168)), AUC(0-infinity), and C(max). Plasma cyclobenzaprine T(max), terminal elimination t(1/2), and adverse events (AEs) were also assessed.


RESULTS
Sixteen subjects (9 women, 7 men) were randomized to receive cyclobenzaprine 15 mg or 30 mg; 13 (81.3%) were white and 3 (18.8%) were black. Mean age and weight were 30.2 years and 70.7 kg, respectively. The shapes of the pharmacokinetic profiles for CER 15 and 30 mg were parallel. Mean observed values for dose-dependent pharmacokinetic parameters of CER 15 and 30 mg were as follows: AUC(0-168), 318.3 and 736.6 ng . h/mL, respectively; AUC(0-infinity)), 354.1 and 779.9 ng . h/mL; and C(max), 8.3 and 19.9 ng/mL. Dose-independent parameters were comparable across doses. Median observed Tmax was 6.0 hours for both CER doses; mean t(1/2) was 33.4 hours for CER 15 mg and 32.0 hours for CER 30 mg. The bioavailability of the 2 doses, as indicated by the least squares mean AUC(0-infinity), was 330.3 ng . h/mL for CER 15 mg and 755.1 ng . h/mL for CER 30 mg. During the CER 15-mg treatment sequence, 5 subjects experienced 5 AEs (headache, dizziness, musculoskeletal pain, dermatitis, and glossodynia); during the CER 30-mg treatment sequence, 2 subjects experienced 2 AEs (somnolence and dysmenorrhea). All AEs were mild in intensity. No serious AEs occurred during the study.


CONCLUSIONS
Once-daily CER 15 and 30 mg exhibited similarly shaped pharmacokinetic profiles. AUC(0-168), AUC(0-infinity)), and C(max) values for the 30-mg dose were approximately double those for the 15-mg dose, a result consistent with previously reported data on the dose proportionality of cyclobenzaprine immediate release.
Darwish
Mona
M
Department of Clinical Pharmacology, Cephalon, Inc., Frazer, Pennsylvania, USA. mdarwish@cephalon.com
Chang
Steven
S
Hellriegel
Edward T
ET
D000293:Adolescent; D000328:Adult; D000639:Amitriptyline / Q000008:administration & dosage / Q000009:adverse effects / Q000031:analogs & derivatives* / Q000493:pharmacokinetics; D019540:Area Under Curve; D001682:Biological Availability; D018592:Cross-Over Studies; D003692:Delayed-Action Preparations; D004305:Dose-Response Relationship, Drug; D004311:Double-Blind Method; D005260:Female; D006207:Half-Life; D006801:Humans; D008297:Male; D009125:Muscle Relaxants, Central / Q000008:administration & dosage / Q000009:adverse effects / Q000493:pharmacokinetics*; D055815:Young Adult
D003692:Delayed-Action Preparations; D009125:Muscle Relaxants, Central; D000639:Amitriptyline; C004704:cyclobenzaprine