Pharmacokinetic Interaction Between Rosuvastatin, Telmisartan, and Amlodipine in Healthy Male Korean Subjects: A Randomized, Open-label, Multiple-dose, 2-period Crossover Study

Son, Mijeong; Guk, Jinju; Kim, Yukyung; Chae, Dong Woo; Heo, Young-A; Soh, D.-J.; Park, Kyungsoo

doi:10.1016/j.clinthera.2016.06.011

Cited by 13 publications

(7 citation statements)

References 25 publications

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“…The increased C max,ss and AUC τ,ss values of rosuvastatin reported in this study when rosuvastatin is administered with telmisartan/amlodipine are consistent with previous studies 14,15. The pharmacokinetic parameters of amlodipine were unchanged, also consistent with previous studies.…”

Section: Discussionsupporting

confidence: 92%

“…However, unlike previous reports, rosuvastatin did not affect the pharmacokinetic parameters of telmisartan when administered concurrently in this study. The change in the absorption phase of rosuvastatin is evident (Figure 1) with a shortened T max,ss , and the mechanism of this change was speculated to be due to intervention in hepatic uptake and a possible change to biliary excretion transporters 15…”

Section: Discussionmentioning

confidence: 99%

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

Moon¹,

Jeon²,

Jang³

et al. 2019

DDDT

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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.

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Section: Discussionsupporting

confidence: 92%

Section: Discussionmentioning

confidence: 99%

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

Moon¹,

Jeon²,

Jang³

et al. 2019

DDDT

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show abstract

“…Both the C max,ss and AUC τ,ss of rosuvastatin showed statistically significant changes and their 90% CIs did not meet the equivalence criteria. The change in the absorption phase of rosuvastatin is evident with a shortened T max,ss , and the mechanism of this change was speculated to be due to intervention in hepatic uptake and a possible change to biliary excretion transporters 24 …”

Section: Discussionmentioning

confidence: 99%

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

Jin

Kim

Han

et al. 2020

J of Clinical Hypertension

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“…18 The shared transporter in the hepatic uptake and biliary excretion of rosuvastatin and telmisartan was suggested as a possible cause. 18,21,22 However, the single 2-fold increase of the C max,ss was not associated with the efficacy and safety of rosuvastatin. 18,23 To be consistent with previous results, the change in the systemic exposure of telmisartan was mild.…”

Section: Tolerabilitymentioning

confidence: 92%

“…24 Indicated in the case of rosuvastatin, the shared transporter for rosuvastatin and telmisartan may account for the slight increase of telmisartan exposure. 18,21,25 The doses of the study medication were set to the maximum approved standard regimens. 9,11,26 Considering the elimination half-lives of the 3 drugs (∼24 hours), 9,13,26 1-week dosing was enough to achieve steady-state concentrations.…”

Section: Tolerabilitymentioning

confidence: 99%

Pharmacokinetic Interaction Among Ezetimibe, Rosuvastatin, and Telmisartan

Huh

Lee

Lee³

et al. 2021

Clinical Pharm in Drug Dev

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To evaluate the pharmacokinetic interactions among rosuvastatin, ezetimibe, and telmisartan, a randomized, open-label, 3period, 6-sequence crossover study was conducted in healthy subjects. Subjects received one of the following treatments once daily for 7 days in each period with a 1-week washout: a fixed-dose combination of ezetimibe/rosuvastatin 10/20 mg, telmisartan 80 mg, combination therapy of ezetimibe/rosuvastatin 10/20 mg, or telmisartan 80 mg. Blood samples were collected up to 24 hours postdose at steady state. Geometric mean ratios (GMRs) and their 90% confidence intervals (CIs) of the combination therapy to monotherapy for the maximum plasma concentration (C max,ss ), and the area under the time-concentration curve within a dosing interval at steady state (AUC tau,ss ) were estimated. Among the 36 randomized subjects, 31 subjects completed the study. The GMRs and 90%CIs of C max,ss and AUC tau,ss of total ezetimibe were not significantly altered. The C max,ss of free ezetimibe was increased (

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Pharmacokinetic Interaction Between Rosuvastatin, Telmisartan, and Amlodipine in Healthy Male Korean Subjects: A Randomized, Open-label, Multiple-dose, 2-period Crossover Study

Cited by 13 publications

References 25 publications

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

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

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

Pharmacokinetic Interaction Among Ezetimibe, Rosuvastatin, and Telmisartan

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