Bioavailability of a controlled-release cyclobenzaprine tablet and influence of a high fat meal on bioavailability.
OBJECTIVE
To evaluate the systemic bioavailability of a new controlled release cyclobenzaprine tablet, and the influence of a high fat meal on its bioavailability.


METHODS
24 and 12 healthy male subjects were recruited for the bioavailability and influence of diet studies, respectively. Experimental design for both studies was an open randomized, 2-period, single dose, crossover study. In the bioavailability study, each subject received in different occasions, a single oral dose of cyclobenzaprine of immediate (10 mg) or controlled release (20 mg) tablet, followed by a 2-week washout period. In the influence of diet study, the volunteers received the controlled-release tablet concomitantly with a high fat meal or in a state of fasting.


RESULTS
In the bioavailability study, plasma cyclobenzaprine profiles were in agreement with a controlled release system. This formulation presented a 92.8% of relative bioavailability (IC 85.5 - 105%) and a significant reduction in Cmax (IC 58 - 65.5%), when compared with equal dose of the immediate release tablet. The presence of food increased AUC (11.6%) and Cmax (48%). For both parameters the calculated 90% confidence interval was not in the bioequivalence interval, 97.4 - 125.8% for AUC and 111.7 - 184.2% for Cmax.


CONCLUSIONS
The controlled release tablet showed a relative bioavailability comparable with equal dose of the immediate release product and produced a significantly lower Cmax, as expected in a controlled release formulation. The concomitant administration of the tablet with a high fat meal produced an increase on its bioavailability, mainly in Cmax, with no evidence of dose-dumping.
Center for Development in Pharmaceutical Technology, Department of Science and Pharmaceutical Technology, Faculty of Chemical and Pharmaceutical Sciences, University of Chile, Santiago de Chile.
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D000328:Adult; D000639:Amitriptyline / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000493:pharmacokinetics; D019540:Area Under Curve; D001682:Biological Availability; D018592:Cross-Over Studies; D003692:Delayed-Action Preparations; D004041:Dietary Fats / Q000008:administration & dosage*; D018565:Food-Drug Interactions; D006801:Humans; D008297:Male; D009125:Muscle Relaxants, Central / Q000008:administration & dosage / Q000493:pharmacokinetics*; D013607:Tablets; D055815:Young Adult
D003692:Delayed-Action Preparations; D004041:Dietary Fats; D009125:Muscle Relaxants, Central; D013607:Tablets; D000639:Amitriptyline; C004704:cyclobenzaprine