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

Abstract

Objective: To compare the bioavailability of single dose ibuprofen 200 mg and pseudoephedrine hydrochloride 30 mg administered alone or in combination as an oral suspension. Methods: 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 (Cmax) and area under the plasma concentration-time curve (AUC) from time zero to last measurable concentration (AUC0-t) and extrapolated to infinity (AUC0-∞) 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 Cmax and AUC were within the predetermined range of 80-125%, in accordance with regulatory requirements. Results: For the test formulation, the ibuprofen gMean Cmax was 17.0 μg/mL (vs. 18.1 μg/mL for reference-A), AUC0-t was 57.1 (vs. 60.0 μgh/mL), and AUC0-∞ was 59.9 μgh/mL (vs. 63.1 μgh/mL). The 90% CIs for the ratio (test/reference-A) were 81.0-108.1% for Cmax, 91.5-98.4% for AUC0-t and 91.6-97.9% for AUC0-∞. For pseudoephedrine, the gMean Cmax for the test formulation was 97.2 ng/mL (vs. 98.5 ng/mL for reference-B), AUC0-t was 878.4 (vs. 842.8 ngh/mL) and AUC0-∞ was 907.8 ngh/mL (vs. 868.3 ngh/mL). The 90% CIs for the ratio (test/reference-B) were 92.4-106.9% for Cmax, 97.7-111.0% for AUC0-t and 97.9-111.3% for AUC0-∞. All treatments were well tolerated. Conclusion: 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. © 2014 Kale.