Mona Darwish1, Fang Xie. 1. Department of Clinical Pharmacology, Cephalon, Inc., Frazer, Pennsylvania, USA.
Abstract
BACKGROUND AND OBJECTIVE: Food can alter the bioavailability of the controlled-release formulations of many different drugs. This study assessed the effect of food on the pharmacokinetics of once-daily cyclobenzaprine extended-release (CER) in healthy adult subjects. METHODS:Healthy adult volunteers were randomized in an open-label, two-period crossover design to receive a single dose of CER 30 mg on days 1 and 15 (separated by a 14-day drug washout) in either the fed or the fasted state. Pharmacokinetic measures included area under the plasma cyclobenzaprine concentration versus time curve to 168 hours (AUC(168)) and infinity (AUC(infinity)), maximum plasma cyclobenzaprine concentration (C(max)), time to observed C(max) (t(max)), terminal elimination half-life (t(1/2beta)), and absorption lag time (t(lag)). A food effect, as determined from the C(max) and the AUC, was established if the 90% confidence interval (CI) for the ratio of the mean fed/fasted values fell outside the range of 0.80 to 1.25. Adverse events were monitored throughout the study. RESULTS:Sixteen healthy volunteers were enrolled (eight men, eight women; mean age 29.7 years), and 15 completed the study. No appreciable differences in the shape of the mean plasma cyclobenzaprine concentration versus time profile, t(lag) (2 hours) or t(max) (fed: 8 hours; fasted: 6 hours) were noted for CER 30 mg in the fed and fasted states. The least-squares mean ratio of fed to fasted state was 1.21 for AUC(168) (90% CI 1.11, 1.32), 1.20 for AUC(infinity) (90% CI 1.11, 1.31), and 1.36 for C(max) (90% CI 1.17, 1.57), which suggested a food effect. Most adverse events were mild in intensity and were comparable in the fed and fasted states. CONCLUSION: The results of this study show that an increase in systemic exposure is observed when CER 30 mg is taken with food. CER 30 mg was generally well tolerated, with comparable adverse events in both the fed and the fasted states. The increase in exposure did not appear to impact the tolerability of the formulation.
RCT Entities:
BACKGROUND AND OBJECTIVE: Food can alter the bioavailability of the controlled-release formulations of many different drugs. This study assessed the effect of food on the pharmacokinetics of once-daily cyclobenzaprine extended-release (CER) in healthy adult subjects. METHODS: Healthy adult volunteers were randomized in an open-label, two-period crossover design to receive a single dose of CER 30 mg on days 1 and 15 (separated by a 14-day drug washout) in either the fed or the fasted state. Pharmacokinetic measures included area under the plasma cyclobenzaprine concentration versus time curve to 168 hours (AUC(168)) and infinity (AUC(infinity)), maximum plasma cyclobenzaprine concentration (C(max)), time to observed C(max) (t(max)), terminal elimination half-life (t(1/2beta)), and absorption lag time (t(lag)). A food effect, as determined from the C(max) and the AUC, was established if the 90% confidence interval (CI) for the ratio of the mean fed/fasted values fell outside the range of 0.80 to 1.25. Adverse events were monitored throughout the study. RESULTS: Sixteen healthy volunteers were enrolled (eight men, eight women; mean age 29.7 years), and 15 completed the study. No appreciable differences in the shape of the mean plasma cyclobenzaprine concentration versus time profile, t(lag) (2 hours) or t(max) (fed: 8 hours; fasted: 6 hours) were noted for CER 30 mg in the fed and fasted states. The least-squares mean ratio of fed to fasted state was 1.21 for AUC(168) (90% CI 1.11, 1.32), 1.20 for AUC(infinity) (90% CI 1.11, 1.31), and 1.36 for C(max) (90% CI 1.17, 1.57), which suggested a food effect. Most adverse events were mild in intensity and were comparable in the fed and fasted states. CONCLUSION: The results of this study show that an increase in systemic exposure is observed when CER 30 mg is taken with food. CER 30 mg was generally well tolerated, with comparable adverse events in both the fed and the fasted states. The increase in exposure did not appear to impact the tolerability of the formulation.
Authors: Tatiane Maria de Lima Souza Brioschi; Simone Grigoleto Schramm; Eunice Kazue Kano; Eunice Emiko Mori Koono; Ting Hui Ching; Cristina Helena Dos Reis Serra; Valentina Porta Journal: Biomed Res Int Date: 2013-09-16 Impact factor: 3.411