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

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.

Prevalence of polypharmacy and risk of potential drug-drug interactions among hospitalized patients with emphasis on the pharmacokinetics

“…The software characterizes it as insignificant (B/minor), which has been confirmed in clinical trials. 28 , 29 The given examples were intended to present the complexity and difficulties in predicting, evaluating, and managing pPKDDIs. In most cases, they require a special approach.…”

Efficacy and safety of co‐administered telmisartan/amlodipine and rosuvastatin in subjects with hypertension and dyslipidemia

“…Our phase 1 trial have shown no statistically significant effect of co‐administration on telmisartan pharmacokinetics 23 . The geometric least‐square mean (GLSM) ratios and 90% CIs of telmisartan were 0.9829 (0.8334‐1.1590) for C max,ss and 1.0003 (0.9342‐1.0710) for AUC τ,ss .…”