AUTHOR=Kale Prashant , Agrawal Yadvendra K. 

TITLE=Pharmacokinetics of single oral dose trazodone: a randomized, two-period, cross-over trial in healthy, adult, human volunteers under fed condition

JOURNAL=Frontiers in Pharmacology

VOLUME=6

YEAR=2015

URL=https://www.frontiersin.org/journals/pharmacology/articles/10.3389/fphar.2015.00224

DOI=10.3389/fphar.2015.00224

ISSN=1663-9812

ABSTRACT=<p><bold>Objective:</bold> To assess the bioequivalence of single dose trazodone hydrochloride USP 100 mg tablets administered as an oral dose under fed condition.</p><p><bold>Methods:</bold>This study was an open-label, balanced, randomized, two-sequence, two-treatment, two-period, single oral dose, crossover bioequivalence study in healthy, adult, human subjects under fed conditions. After an overnight fast of at least 10 h, the subjects were served a high fat and high calorie vegetarian breakfast, which they were required to consume within 30 min. A single oral dose (100 mg) of either the test or the reference product was administered to the subjects. The primary pharmacokinetic parameters, maximum plasma concentration (C<sub>max</sub>) and area under the plasma concentration–time curve (AUC) from time zero to last measurable concentration (AUC<sub>0−<italic>t</italic></sub>) and extrapolated to infinity (AUC<sub>0−∞</sub>) were compared by an analysis of variance using log-transformed data. Bioequivalence was concluded if the 90% confidence intervals (CIs) of the adjusted geometric mean (gMean) ratios for C<sub><italic>max</italic></sub> and AUC were within the predetermined range of 80–125%, in accordance with regulatory requirements.</p><p><bold>Results:</bold>For the test formulation, the trazodone gMean C<sub>max</sub> was 1480.9 ng/mL (vs. 1520.2 ng/mL for reference), AUC<sub>0−<italic>t</italic></sub> was 18193.0 ng·h/mL (vs. 18209.8 ng·h/mL) and AUC<sub>0−∞</sub> was 19346.3 ng·h/mL (vs. 19393.4 ng·h/mL). The 90% CIs for the ratio (test/reference) were 93.0–102.0% for C<sub>max</sub>, 96.7–103.2% for AUC<sub>0−<italic>t</italic></sub> and 96.1–103.5% for AUC<sub>0−∞</sub>. There were no deaths or serious adverse events during the conduct of the study.</p><p><bold>Conclusion:</bold>Test product when compared with the Reference product meets the bioequivalence criteria with respect to the extent of absorption of trazodone under fed condition.</p>