OBJECTIVE: A 24-h extended-release formulation of fexofenadine HCl 180 mg/pseudoephedrine HCl 240 mg (FEX 180 mg/PSE 240 mg) has recently been approved by the US Food and Drug Administration for symptom relief of seasonal allergic rhinitis, including nasal congestion. When considering a combination formulation, it is important to confirm that the metabolism and pharmacokinetics of the drugs remain unchanged when combined. Thus, the aim of this study was to evaluate single-dose and steady-state bioequivalence of FEX 180 mg/PSE 240 mg 24-h compared with the individual formulations taken concurrently. RESEARCH DESIGN AND METHODS: This was an open-label, randomized, two-treatment, two-period, 10-day, crossover study. In Treatment A, healthy subjects received a single, oral dose of FEX 180 mg/PSE 240 mg combination tablet on Day 1 followed by 6 days of once-daily dosing beginning on Day 4. Participants in Treatment B were concurrently administered a single oral dose of FEX 180 mg immediate-release tablet and a PSE 240 mg extended-release tablet with a similar dosing schedule. After an 8-day washout period, subjects crossed over to the alternate treatment. Plasma concentrations of FEX and PSE were determined using high-performance liquid chromatography/mass spectrometry. RESULTS: Pharmacokinetic parameters AUC0-infinity1 and Cmax1 following a single-dose (Day 1, dose 1), Cmax7, AUC0-24(7) at steady-state and Cmin7 measured at the end of the dosing interval (Day 9, dose 7) revealed bioequivalence between FEX 180 mg/PSE 240 mg combination tablet and the individual components taken concurrently. The 90% confidence intervals for the treatment ratios fell entirely within the bioequivalence range (80% to 125%). The combination tablet was well tolerated by all subjects, with a safety profile comparable to the individual components. CONCLUSIONS: These findings demonstrate that the pharmacokinetics of the new 24-h FEX 180 mg/PSE 240 mg combination formulation are bioequivalent to the concurrent administration of the individual drug components. Furthermore, both treatments were well tolerated in this population.
RCT Entities:
OBJECTIVE: A 24-h extended-release formulation of fexofenadine HCl 180 mg/pseudoephedrine HCl 240 mg (FEX 180 mg/PSE 240 mg) has recently been approved by the US Food and Drug Administration for symptom relief of seasonal allergic rhinitis, including nasal congestion. When considering a combination formulation, it is important to confirm that the metabolism and pharmacokinetics of the drugs remain unchanged when combined. Thus, the aim of this study was to evaluate single-dose and steady-state bioequivalence of FEX 180 mg/PSE 240 mg 24-h compared with the individual formulations taken concurrently. RESEARCH DESIGN AND METHODS: This was an open-label, randomized, two-treatment, two-period, 10-day, crossover study. In Treatment A, healthy subjects received a single, oral dose of FEX 180 mg/PSE 240 mg combination tablet on Day 1 followed by 6 days of once-daily dosing beginning on Day 4. Participants in Treatment B were concurrently administered a single oral dose of FEX 180 mg immediate-release tablet and a PSE 240 mg extended-release tablet with a similar dosing schedule. After an 8-day washout period, subjects crossed over to the alternate treatment. Plasma concentrations of FEX and PSE were determined using high-performance liquid chromatography/mass spectrometry. RESULTS: Pharmacokinetic parameters AUC0-infinity1 and Cmax1 following a single-dose (Day 1, dose 1), Cmax7, AUC0-24(7) at steady-state and Cmin7 measured at the end of the dosing interval (Day 9, dose 7) revealed bioequivalence between FEX 180 mg/PSE 240 mg combination tablet and the individual components taken concurrently. The 90% confidence intervals for the treatment ratios fell entirely within the bioequivalence range (80% to 125%). The combination tablet was well tolerated by all subjects, with a safety profile comparable to the individual components. CONCLUSIONS: These findings demonstrate that the pharmacokinetics of the new 24-h FEX 180 mg/PSE 240 mg combination formulation are bioequivalent to the concurrent administration of the individual drug components. Furthermore, both treatments were well tolerated in this population.