The study was approved by the local Ethical Committee and included 26 healthy subjects: 13 males and 13 females. It was performed with two different 10 mg cyclobenzaprine tablets: the test product (Miosan of Apsen in Brazil) and the reference product (Flexeril of Merck & Co). It was a randomized, open and crossover study with a single oral dose, two periods and two sequences design. Tablets were administered after an overnight fasting with 200 mL of water. Fasting continued for a further four-hour period. Subjects were provided with standard meals after four hours (lunch), seven hours (snack) and 11 hours (dinner) after drug administration. Blood samples were collected according to a schedule which included a blank before-drug sample just prior to drug administration and samples at 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 12, 24, 48, 72, 96, 144, 192 and 240 hours after drug administration. Plasmatic cyclobenzaprine was quantified by validated method using high-pressure liquid chromatography (HPLC) with mass spectrometric (MS) detection: LC-MS/MS.

The average plasmatic decay curves of test (Miosan) and reference (Flexeril) products were similar ASC0-t (test: 193,00 ngxh/mL; reference: 191,66 ngxh/mL), in the same way that absorption parameters Cmax (test: 7,16 ng/mL; reference: 6,95 ng/mL), tmax (test: 4,61 h; reference: 4,48 h), Ka (reference: 0,79; test: 0,67) e t(1/2)a (reference: 1,79 h; test: 2,02 h). The elimination parameters Cl (test: 31,15 L/h; reference: 31,73 L/h), Vd (test: 1378,54 L e reference (1357,87 L), kb (reference: 0,08; test: 0,08), t(1/2)β (reference: 9,43 h; test: 9,20 h), kg (reference: 0,02; test: 0,02) e t(1/2)γ (reference: 32,92 h; test: 31,67 h) were similar between products too. The multivariate analysis accomplished through analysis of variance (ANOVA) for the assessment of product, group and period effects, revealed the absence of any of these effects in the present study, indicating that the crossover design was properly performed. The 90% confidence intervals (90% CI) for the ratio of Cmax(93.0–112.0 %), AUC0-t(92.6–111.1 %) and AUC0∞ (93.1–110.4 %) values for the test and reference products fell within the 80–125% interval, as has been proposed for bioequivalent products by regulatory agencies such as the US FDA, the European Medicines Agency and the Brazilian Agência Nacional de Vigilância Sanitária (ANVISA). Statistical analysis of Cmax, AUC0-t e AUC0-∞ parameters indicated no significant difference between two brands of 10 mg cyclobenzaprine hydrochloride products. Based on the results of this study, they concluded that the two products are bioequivalent and can be considered interchangeable in medical practice.

Reference:

Tatiane Maria de Lima Souza Brioschi et al. Pharmacokinetics and bioequivalence evaluation of cyclobenzaprine tablets. Poster at the 2008 World Congress of Pharmacy and Pharmaceutical Sciences in Basel, Switzerland. 29 August – 4 September 2008