Lack of association between MRP2 C-24T variant and the pharmacokinetics of fexofenadine

Purpose: Fexofenadine is a selective histamine H₁-receptor antagonist and is used for the treatment of seasonal allergic rhinitis and chronic idiopathic urticaria. In a previous animal study showed that the biliary excretion of fexofenadine is mainly mediated by Mrp2, an efflux transporter, in mice. MRP2 C-24T single nucleotide polymorphism (SNP) is known to decrease the efflux activity and function. We investigated the effects of MRP2 C-24T variant on the pharmacokinetics of fexofenadine in healthy Korean volunteers.

Methods: Twelve subjects were selected and they were divided into two different groups according to MRP2 C-24T genotype, MRP2 -24CC (CC type, n=8) and MRP2 -24TT (TT type, n=4). After overnight fasting, each subject received a single oral dose of 180 mg fexofenadine. Blood samples were collected up to 24 hr after drug intake, and the plasma concentrations of fexofenadine were determined by using LC-MS/MS system.

Results: C_max of fexofenadine in the TT type was slightly higher than that in the CC type (765.0 ± 396.5 ng/mL vs. 559.5 ± 246.3 ng/mL, respectively). However, this difference was not statistically significant. Other pharmacokinetic parameters of fexofenadine between two genotype groups were also not significantly different AUC_inf of fexofenadine in the CC type and TT type was 3632.9 ± 1348.1 ng·hr/mL and 3933.2 ± 1388.5 ng·hr/mL, respectively.

Conclusion: MRP2 C-24T genetic variant is not likely to influence the pharmacokinetics of fexofenadine.