Pharmacokinetic interactions between telmisartan/amlodipine and rosuvastatin after multiple oral administrations in healthy Korean male subjects

Abstract

Purpose

Hypertension and dyslipidemia are major risk factors for cardiovascular diseases, and reduction of cardiovascular risks can be achieved by combining antihypertensive therapy with statins. The objective of this study was to evaluate the pharmacokinetic interaction between telmisartan/amlodipine fixed dose combination and rosuvastatin in healthy Korean male volunteers.

Patients and methods

An open-label, two-cohort, multiple-dose, single-sequence crossover study was conducted in healthy male subjects. In Cohort 1, the subjects were administered one tablet of telmisartan/amlodipine 80 mg/5 mg once daily for 14 days with or without one tablet of rosuvastatin 20 mg once daily. In Cohort 2, the subjects were administered one tablet of rosuvastatin 20 mg once daily for 14 days with or without one tablet of telmisartan/amlodipine 80 mg/5 mg once daily. Serial blood samples were collected up to 24 hrs post-dose on the 9th and 14th days in Cohort 1 and on the 5th and 14th days in Cohort 2. Plasma drug concentrations were measured by liquid chromatography/tandem mass spectrometry. Pharmacokinetic parameters, including maximum plasma concentration at steady state (C_max,ss) and area under the plasma concentration versus time curve over dosing interval (AUC_τ,ss), were determined by non-compartmental analysis. The geometric least-square mean (GLSM) ratios and associated 90% confidence intervals (CIs) of log-transformed C_max,ss and AUC_τ,ss for separate or concurrent therapy were calculated to evaluate pharmacokinetic interactions.

Results

Thirty-eight subjects from Cohort 1 and nineteen subjects from Cohort 2 completed the study. The GLSM ratios and 90% CIs of C_max,ss and AUC_τ,ss, were 0.9829 (0.8334–1.1590) and 1.0003 (0.9342–1.0710) for telmisartan; 0.9908 (0.9602–1.0223) and 1.0081 (0.9758–1.0413) for amlodipine; and 2.2762 (2.0113–2.5758) and 1.3261 (1.2385–1.4198) for rosuvastatin, respectively.

Conclusion

The pharmacokinetic parameters of telmisartan/amlodipine, but not rosuvastatin, met the pharmacokinetic equivalent criteria. The increase in systemic exposure to rosuvastatin caused by telmisartan/amlodipine co-administration would not be clinically significant in practice. Nevertheless, an appropriately designed two-sequence crossover study is needed to confirm the results of this study.

Keywords:

• drug–drug interactions
• pharmacokinetics
• phase I
• antihypertensive
• statins

Funding

This study was sponsored by Yuhan Corporation, Republic of Korea.

Data sharing statement

The individual deidentified participant data will not be shared due to the sponsor’s (Yuhan Corporation) request.

Author contributions

All authors contributed toward data analysis, drafting and critically revising the paper, gave final approval of the version to be published, and agree to be accountable for all aspects of the work.

Disclosure

Yeji Lim is a paid employee of Yuhan Corporation. The authors report no other conflicts of interest in this work.