PMID- 19243711 OWN - NLM STAT- MEDLINE DCOM- 20090407 LR - 20131121 IS - 0149-2918 (Print) IS - 0149-2918 (Linking) VI - 31 IP - 1 DP - 2009 Jan TI - 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. PG - 108-14 LID - 10.1016/j.clinthera.2009.01.014 [doi] AB - 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. FAU - Darwish, Mona AU - Darwish M AD - Department of Clinical Pharmacology, Cephalon, Inc., Frazer, Pennsylvania, USA. mdarwish@cephalon.com FAU - Chang, Steven AU - Chang S FAU - Hellriegel, Edward T AU - Hellriegel ET LA - eng PT - Comparative Study PT - Journal Article PT - Randomized Controlled Trial PT - Research Support, Non-U.S. Gov't PL - United States TA - Clin Ther JT - Clinical therapeutics JID - 7706726 RN - 0 (Delayed-Action Preparations) RN - 0 (Muscle Relaxants, Central) RN - 1806D8D52K (Amitriptyline) RN - 69O5WQQ5TI (cyclobenzaprine) SB - IM MH - Adolescent MH - Adult MH - Amitriptyline/administration & dosage/adverse effects/*analogs & derivatives/pharmacokinetics MH - Area Under Curve MH - Biological Availability MH - Cross-Over Studies MH - Delayed-Action Preparations MH - Dose-Response Relationship, Drug MH - Double-Blind Method MH - Female MH - Half-Life MH - Humans MH - Male MH - Muscle Relaxants, Central/administration & dosage/adverse effects/*pharmacokinetics MH - Young Adult EDAT- 2009/02/27 09:00 MHDA- 2009/04/08 09:00 CRDT- 2009/02/27 09:00 PHST- 2008/11/21 00:00 [accepted] PHST- 2009/02/27 09:00 [entrez] PHST- 2009/02/27 09:00 [pubmed] PHST- 2009/04/08 09:00 [medline] AID - S0149-2918(09)00028-9 [pii] AID - 10.1016/j.clinthera.2009.01.014 [doi] PST - ppublish SO - Clin Ther. 2009 Jan;31(1):108-14. doi: 10.1016/j.clinthera.2009.01.014.