AUTHOR=Kale Prashant 

TITLE=Pharmacokinetics and bioavailability of single dose ibuprofen and pseudoephedrine alone or in combination: a randomized three-period, cross-over trial in healthy Indian volunteers

JOURNAL=Frontiers in Pharmacology

VOLUME=5

YEAR=2014

URL=https://www.frontiersin.org/journals/pharmacology/articles/10.3389/fphar.2014.00098

DOI=10.3389/fphar.2014.00098

ISSN=1663-9812

ABSTRACT=<p><bold>Objective:</bold> To compare the bioavailability of single dose ibuprofen 200 mg and pseudoephedrine hydrochloride 30 mg administered alone or in combination as an oral suspension.</p><p><bold>Methods:</bold> This was a single-center, randomized, single-dose, open-label, 3-period, crossover study. After an overnight fast (≥10 h), 18 healthy male subjects received either ibuprofen 200 mg (reference-A), pseudoephedrine 30 mg (reference-B) or the combination (test-C) as a suspension, on 3 separate visits, with blood sampling up to 36-h post-dose. 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−t</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>max</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 ibuprofen gMean C<sub>max</sub> was 17.0 μg/mL (vs. 18.1 μg/mL for reference-A), AUC<sub>0−t</sub> was 57.1 (vs. 60.0 μg·h/mL), and AUC<sub>0−∞</sub> was 59.9 μg·h/mL (vs. 63.1 μg·h/mL). The 90% CIs for the ratio (test/reference-A) were 81.0–108.1% for C<sub>max</sub>, 91.5–98.4% for AUC<sub>0−t</sub> and 91.6–97.9% for AUC<sub>0−∞</sub>. For pseudoephedrine, the gMean C<sub>max</sub> for the test formulation was 97.2 ng/mL (vs. 98.5 ng/mL for reference-B), AUC<sub>0−t</sub> was 878.4 (vs. 842.8 ng·h/mL) and AUC<sub>0−∞</sub> was 907.8 ng·h/mL (vs. 868.3 ng·h/mL). The 90% CIs for the ratio (test/reference-B) were 92.4–106.9% for C<sub>max</sub>, 97.7–111.0% for AUC<sub>0−t</sub> and 97.9–111.3% for AUC<sub>0−∞</sub>. All treatments were well tolerated.</p><p><bold>Conclusion:</bold> This oral suspension containing ibuprofen and pseudoephedrine combined in a new formulation met the regulatory criterion for bioequivalence compared with oral suspensions containing the individual components.</p>