Effects of genetic variants in UGT1A1, SLCO1B3, ABCB1, ABCC2, ABCG2, ORM1 on PK/PD of telmisartan in Chinese patients with mild to moderate essential hypertension .

Abstract

This study aimed to understand the effects of single nucleotide polymorphisms (SNPs) in UGT1A1, SLCO1B3, ABCB1, ABCC2, ABCG2, and ORM1 on the pharmacokinetics (PK) (plasma concentration) and pharmacodynamics (PD) (blood pressure) of telmisartan in Chinese patients. 58 Han Chinese patients (aged 45 - 72 years) with mild to moderate essential hypertension were included and received 80mg/day telmisartan for 4 weeks. The plasma concentration and genetic variants were determined by LC/MS/MS and MALDI-TOF mass spectrometry, respectively. Multivariable linear analysis was used to examine the relationships between PK/PD and genetic variants. Females showed a significantly higher AUC_last than males (n=22, 4,879.48±3,449.33 h×ng/mL vs. n=36, 2,715.59±2,223.77 h×ng/mL, p=0.047). Amongst all genetic variants investigated, the patients with UGT1A1 rs4124874 AA (n=11, 1,730.51±1,325.79 h×ng/mL) had a significantly lower AUC_last compared with patients with UGT1A1 rs4124874 CC+AC (n=19 + 28, 4,177.44±3,222.11 h×ng/mL and 3,810.82±2,960.43 h×ng/mL, p=0.027). None of the SNPs investigated was associated with the PD responses to telmisartan. Variation of UGT1A1 (rs4124874) affects PK of telmisartan in Chinese patients, highlighting the value of genetic testing in precision medicine as the telmisartan dose could be adjusted based on UGT1A1 genetic variations. .