Allegra pharmacokinetics
The pharmacokinetics of fexofenadine hydrochloride in subjects with seasonal allergic rhinitis and subjects with chronic urticaria were similar to those in healthy subjects.
Absorption
Allegra Tablets: Fexofenadine hydrochloride was rapidly absorbed following oral administration of a single dose of two 60 mg capsules to healthy male subjects with a mean time to maximum plasma concentration occurring at 2.6 hours post-dose. After administration of a single 60 mg capsule to healthy adult subjects, the mean maximum plasma concentration (Cmax) was 131 ng/mL. Following single dose oral administrations of either the 60 and 180 mg tablet to healthy adult male subjects, mean Cmax were 142 and 494 ng/mL, respectively. The tablet formulations are bioequivalent to the capsule when administered at equal doses. Fexofenadine hydrochloride pharmacokinetics are linear for oral doses up to a total daily dose of 240 mg (120 mg twice daily). The administration of the 60 mg capsule contents mixed with applesauce did not have a significant effect on the pharmacokinetics of fexofenadine in adults. Co-administration of 180 mg fexofenadine hydrochloride tablet with a high fat meal decreased the mean area under the curve (AUC) and (Cmax) of fexofenadine by 21 and 20% respectively.
Allegra ODT: Fexofenadine hydrochloride was rapidly absorbed following single-dose oral administration of Allegra ODT 30 mg to healthy adult subjects. The mean maximum plasma concentration (Cmax) was 88.0 ng/mL and occurred at approximately 2.0 hours (Tmax) following oral administration. Allegra ODT 30 mg tablets are bioequivalent to the 30 mg Allegra Tablets. The administrationof Allegra ODT 30 mg with a high-fat meal decreased the AUC and Cmax by approximately 40% and 60% respectively and a 2-hour delay in the time to peak exposure (Tmax) was observed. Allegra ODT should be taken on an empty stomach. The bioavailability of Allegra ODT was comparable whether given with or without water.
Allegra Oral Suspension: A dose of 5 mL of Allegra Oral Suspension containing 30 mg of fexofenadine hydrochloride is bioequivalent to a 30 mg dose of Allegra Tablets. Following oral administration of a 30 mg dose of Allegra Oral Suspension to healthy adult subjects, the mean Cmax was 118.0 ng/mL and occurred at approximately 1.0 hour. The administration of 30 mg Allegra Oral Suspension with a high fat meal decreased the AUC and the mean Cmax by approximately 30 and 47%, respectively in healthy adult subjects.
Distribution
Fexofenadine hydrochloride is 60% to 70% bound to plasma proteins, primarily albumin and α1-acid glycoprotein.
Metabolism
Approximately 5% of the total dose of fexofenadine hydrochloride was eliminated by hepatic metabolism.
Elimination
The mean elimination half-life of fexofenadine was 14.4 hours following administration of 60 mg twice daily in healthy adult subjects.
Human mass balance studies documented a recovery of approximately 80% and 11% of the [14C] fexofenadine hydrochloride dose in the feces and urine, respectively. Because the absolute bioavailability of fexofenadine hydrochloride has not been established, it is unknown if the fecal component represents primarily unabsorbed drug or is the result of biliary excretion.
Special Populations
Pharmacokinetics in renally and hepatically impaired subjects and geriatric subjects, obtained after a single dose of 80 mg fexofenadine hydrochloride, were compared to those from healthy subjects in a separate study of similar design.
Renally Impaired. In subjects with mild to moderate (creatinine clearance 41–80 mL/min) and severe (creatinine clearance 11–40 mL/min) renal impairment, peak plasma concentrations of fexofenadine were 87% and 111% greater, respectively, and mean elimination half-lives were 59% and 72% longer, respectively, than observed in healthy subjects. Peak plasma concentrations in subjects on dialysis (creatinine clearance ≤10 mL/min) were 82% greater and half-life was 31% longer than observed in healthy subjects. Based on increases in bioavailability and half-life, a dose of 60 mg once daily is recommended as the starting dose in adult patients with decreased renal function. For pediatric patients with decreased renal function, the recommended starting dose of fexofenadine is 30 mg once daily for patients 2 to 11 years of age and 15 mg once daily for patients 6 months to less than 2 years of age.
Hepatically Impaired. The pharmacokinetics of fexofenadine hydrochloride in subjects with hepatic disease did not differ substantially from that observed in healthy subjects.
Geriatric Subjects. In older subjects (≥65 years old), peak plasma levels of fexofenadine were 99% greater than those observed in younger subjects (<65 years old). Mean fexofenadine elimination half-lives were similar to those observed in younger subjects.
Pediatric Subjects. A population pharmacokinetic analysis was performed with data from 77 pediatric subjects (6 months to 12 years of age) with allergic rhinitis and 136 adult subjects. The individual apparent oral clearance estimates of fexofenadine were on average 44% and 36% lower in pediatric subjects 6 to 12 years (n=14) and 2 to 5 years of age (n=21), respectively, compared to adult subjects.
Administration of a 15 mg dose of fexofenadine hydrochloride to pediatric subjects 6 months to less than 2 years of age and a 30 mg dose to pediatric subjects 2 to 11 years of age produced exposures comparable to those seen with a dose of 60 mg administered to adults.
Effect of Gender. Across several trials, no clinically significant gender-related differences were observed in the pharmacokinetics of fexofenadine hydrochloride.
