Single-dose and steady-state bioequivalence of fexofenadine and pseudoephedrine combination tablets compared with individual formulations in healthy adults.
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.


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.
Howard
Danny R
DR
Aventis Pharmaceuticals, a member of the sanofi-aventis Group, Bridgewater, NJ 08807, USA. dan.howard@sanofi-aventis.com
Haribhakti
Rajiv
R
Kittner
Barbara
B
Agrawala
Praful
P
D000293:Adolescent; D000316:Adrenergic alpha-Agonists / Q000008:administration & dosage / Q000493:pharmacokinetics*; D000328:Adult; D018592:Cross-Over Studies; D003692:Delayed-Action Preparations; D004338:Drug Combinations; D004359:Drug Therapy, Combination; D004809:Ephedrine / Q000008:administration & dosage / Q000493:pharmacokinetics*; D005260:Female; D006634:Histamine H1 Antagonists / Q000008:administration & dosage / Q000493:pharmacokinetics*; D006801:Humans; D008297:Male; D012221:Rhinitis, Allergic, Perennial / Q000188:drug therapy; D013607:Tablets; D016593:Terfenadine / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000493:pharmacokinetics*; D013810:Therapeutic Equivalency
D000316:Adrenergic alpha-Agonists; D003692:Delayed-Action Preparations; D004338:Drug Combinations; D006634:Histamine H1 Antagonists; D013607:Tablets; D016593:Terfenadine; C093230:fexofenadine; D004809:Ephedrine