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Effects of UGT1A1 Polymorphism, Gender and Triglyceride on the Pharmacokinetics of Telmisartan in Chinese Patients with Hypertension: A Population Pharmacokinetic Analysis

  • Lu Huang
  • Liu Yang
  • Jie Huang
  • Hong-yi Tan
  • Shi-kun Liu
  • Cheng-xian Guo
  • Xiao-cong Zuo
  • Guo-ping YangEmail author
  • Qi PeiEmail author
Original Research Article

Abstract

Background and Objective

Telmisartan is an angiotensin receptor blocker used for the treatment of hypertension. The effects of gender and uridine diphosphate-glycosytransferase 1A1 (UGT1A1) genetic polymorphisms (rs4124874, rs4148323, and rs6742078) on telmisartan plasma concentration and blood pressure in Chinese patients with hypertension have been reported previously. In this study, we aimed to develop a population pharmacokinetic (PopPK) model to quantify the effects of gender and UGT1A1 polymorphisms on the pharmacokinetics of telmisartan.

Methods

Population pharmacokinetic analyses were performed using data collected prospectively from 58 Chinese patients with mild to moderate essential hypertension (aged 45–72 years; 36 men, 22 women) receiving 80 mg/day telmisartan orally for 4 weeks. Blood samples were collected in heparinized tubes at 0, 0.5, 1, and 6 h on day 28 after telmisartan administration. The plasma concentrations and UGT1A1 genetic variants were determined by high-performance liquid chromatography–mass spectrometry and matrix-assisted laser desorption/ionization time-of-flight mass spectrometry, respectively.

Results

A two-compartment pharmacokinetic structural model with first-order elimination and absorption best described the pharmacokinetic characteristics of telmisartan. Gender and triglyceride influenced the apparent oral clearance (CL) of telmisartan. UGT1A1 (rs4124874) affected the bioavailability (F1) of telmisartan. Lower CL and bioavailability resulted in higher plasma concentrations being observed in female subjects with UGT1A1 CC or CA genotype and high triglyceride.

Conclusion

A PopPK model of telmisartan was established to confirm that UGT1A1 genotype, gender and triglyceride can affect the pharmacokinetics of telmisartan in Chinese patients with hypertension. Our findings can provide relevant pharmacokinetic parameters for further study of telmisartan.

Notes

Compliance with Ethical Standards

Funding

The study was supported by grants from the National Scientific Foundation of China (No. 81302851), International Science & Technology Cooperation Program of China (Grant 2014DFA30900); Health Department Foundation of Hunan Province (132013-028), The New Xiangya Talent Projects of the Third Xiangya Hospital of Central South University (No. JY201616).

Conflict of Interest

All authors have no conflicts of interests to declare.

Ethical Approval

All procedures performed in studies involving human participants were in accordance with the ethical standards of the institutional and/or national research committee and with the 1964 Helsinki Declaration and its later amendments or comparable ethical standards. The study was approved by the Ethics Committee of the Third Xiangya Hospital of Central South University.

Informed Consent

Informed consent was obtained from all individual participants included in the study.

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Copyright information

© Springer Nature Switzerland AG 2019

Authors and Affiliations

  1. 1.Department of Pharmacy, The Third Xiangya HospitalCentral South UniversityChangshaPeople’s Republic of China
  2. 2.Reproductive and Genetic Hospital of Citic-XiangyaChangshaPeople’s Republic of China
  3. 3.Department of Pharmacy and Center of Clinical Pharmacology, The Third Xiangya HospitalCentral South UniversityHunanPeople’s Republic of China

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