Fexofenadine pharmacokinetics and molecular data

Pharmacokinetics
Absorption Distribution Elimination Metabolism Special populations Seasonal allergic rhinitis (SAR) and chronic idiopathic urticaria (CIU) patients Geriatric subjects Pediatric patients Renal impairment Hepatic impairment Effect of gender

Absorption
Fexofenadine hydrochloride was rapidly absorbed following oral administration of a single dose of two 60 mg capsules to healthy male volunteers 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 subjects, the mean maximum plasma concentration was 131 ng/mL. Following single dose oral administrations of either the 60 or 180 mg tablet to healthy, adult male volunteers, mean maximum plasma concentrations 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. Return to top

Distribution
Fexofenadine hydrochloride is 60% to 70% bound to plasma proteins, primarily albumin and α1-acid glycoprotein. Return to top

Elimination
The mean elimination half-life of fexofenadine was 14.4 hours following administration of 60mg, twice daily, in normal volunteers. 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 unabsorbed drug or the result of biliary excretion.

Metabolism
Approximately 5% of the total oral dose was metabolized. Return to top

Special populations
Special population pharmacokinetics (for geriatric subjects, renal and hepatic impairment), obtained after a single dose of 80 mg fexofenadine hydrochloride, were compared to those for normal subjects from a separate study of similar design. While subject weights were relatively uniform between studies, these adult special population patients were substantially older than the healthy, young volunteers. Thus, an age effect may be confounding the pharmacokinetic differences observed in some of the special populations. Return to top

Seasonal allergic rhinitis (SAR) and chronic idiopathic urticaria (CIU) patients
The pharmacokinetics of fexofenadine hydrochloride in seasonal allergic rhinitis and chronic idiopathic urticaria patients were similar to those in healthy subjects. Return to top

Geriatric subjects
In older subjects (≥65 years old), peak plasma levels of fexofenadine were 99% greater than those observed in normal volunteers (<65 years old). Mean elimination half lives were similar to those observed in normal volunteers. Return to top

Pediatric patients
Cross study comparisons indicated that fexofenadine hydrochloride area under the curve (AUC) following oral administration of a 60 mg dose to 7-12 year old pediatric allergic rhinitis patients was 56% greater compared to healthy adult subjects given the same dose. Plasma exposure in pediatric patients given 30 mg fexofenadine hydrochloride is comparable to adults given 60 mg. Return to top

Renal impairment
In patients with mild to moderate (creatinine clearance 41-80 mL/min) and severe (creatinine clearance 11-40 mL/min) renal impairment, peak plasma levels of fexofenadine were 87% and 111% greater, respectively, and mean elimination half-lives were 59% and 72% longer, respectively, than observed in normal volunteers. Peak plasma levels in patients on dialysis (creatinine clearance ≤10 mL/min) were 82% greater and half-life was 31% longer than observed in normal volunteers. Based on increases in bioavailability and half-life, a dose of 60 mg once daily is recommended as the starting dose in patients with decreased renal function. Return to top

Hepatic impairment
The pharmacokinetics of fexofenadine hydrochloride in patients with hepatic disease did not differ substantially from that observed in healthy patients. Return to top

Effect of gender
Across several trials, no clinically significant gender-related differences were observed in the pharmacokinetics of fexofenadine hydrochloride. Return to top