Effects of ABCC2 C-24T genetic variant on the pharmacokinetics of valsartan in healthy Koreans

Purpose: Valsartan, a selective angiotensin II receptor type-1 (AT1) antagonist, is widely used for the treatment of essential hypertension. Valsartan is minimally metabolized in humans, and more than 80% of absorbed valsartan is excreted in feces, primarily as unchanged drug. It is reported that valsartan is a substrate of MRP2, an efflux transporter enconded by ABCC2 gene. We investigated the effects of ABCC2 C-24T genetic variant on the pharmacokinetics of valsartan.

Methods: Eleven healthy volunteers were selected and they were divided into two groups according to ABCC2 C-24T genotype, -24CC type (CC type, n=6) and -24TT type (TT type, n=5). After overnight fasting, each subject received a single oral dose of 80 mg valsartan. Blood samples were collected up to 24 hours after drug intake, and the plasma concentrations of valsartan were determined by using HPLC system with fluorescence detection.

Results: C_max and AUC_inf of valsartan in TT type (3.2 ± 2.0 ng/mL and 20.1 ± 13.8 ng∙hr/mL, respectively) were higher than those in CC type (2.2 ± 0.8 ng/mL and 11.0 ± 3.6 ng∙hr/mL, respectively). Oral clearance (CL/F) of valsartan in TT type was lower than that in CC type (6.4 ± 5.0 L/hr vs. 8.7 ± 5.3 L/hr). However, all of these differences were not significant, maybe due to relatively small number of subjects in each group.

Conclusion: ABCC2 C-24T variant can be a possible genetic determinant that affects the disposition of valsartan. Further studies will establish more clear relationship between ABCC2 genotype and valsartan pharmacokinetics.