Dose proportionality and comparison of single and multiple dose pharmacokinetics of fexofenadine (MDL 16 455) and its enantiomers in healthy male volunteers

✍ Scribed by Doris K. Robbins; Mark A. Castles; David J. Pack; Vijay O. Bhargava; Scott J. Weir

• Publisher: John Wiley and Sons
• Year: 1998
• Tongue: English
• Weight: 225 KB
• Volume: 19
• Category: Article
• ISSN: 0142-2782
• DOI: 10.1002/(sici)1099-081x(199810)19:7<455::aid-bdd130>3.0.co;2-w

✦ Synopsis

The pharmacokinetics and dose proportionality of fexofenadine, a new non-sedating antihistamine, and its enantiomers were characterized after single and multiple-dose administration of its hydrochloride salt. A total of 24 healthy male volunteers (31 98 years) received oral doses of 20, 60, 120 and 240 mg fexofenadine HCl in a randomized, complete four-period cross-over design. Subjects received a single oral dose on day 1, and multiple oral doses every 12 h on day 3 through the morning on day 7. Treatments were separated by a 14-day washout period. Serial blood and urine samples were collected for up to 48 h following the first and last doses of fexofenadine HCl. Fexofenadine and its R(+) and S(-) enantiomers were analysed in plasma and urine by validated HPLC methods. Fexofenadine pharmacokinetics were linear across the 20-120 mg dose range, but a small disproportionate increase in area under the plasma concentration-time curve (AUC) ( B 25%) was observed following the 240 mg dose. Singledose pharmacokinetics of fexofenadine were predictive of steady-state pharmacokinetics. Urinary elimination of fexofenadine played a minor role (10%) in the disposition of this drug. A 63:37 steady-state ratio of R( +) and S( -) fexofenadine was observed in plasma. This ratio was essentially constant across time and dose. R( +) and S( -) fexofenadine were eliminated into urine in equal rates and quantities. All doses of fexofenadine HCl were well tolerated after single and multiple-dose administration.