<p>Pharmacokinetic comparison of a fixed-dose combination versus concomitant administration of amlodipine, olmesartan, and rosuvastatin in healthy adult subjects</p>

Abstract

Objective: The aim of this study was to compare the pharmacokinetic (PK) and safety profiles of a fixed dose combination (FDC) formulation and co-administration of amlodipine, olmesartan, and rosuvastatin. Materials and methods: This study was an open-label, randomized, cross-over design conducted in healthy male volunteers. All subjects received either a single FDC tablet containing amlodipine 10 mg/olmesartan 40 mg/rosuvastatin 20 mg, or were co-administered an FDC tablet containing amlodipine 10 mg/olmesartan 40 mg and a tablet containing rosuvastatin 20 mg, for each period, with 14-day washout periods. Plasma concentrations of amlodipine, olmesartan, and rosuvastatin were measured by liquid chromatography tandem mass spectrometry. Safety was evaluated by measuring vital signs, clinical laboratory parameters, physical examinations, and medical interviews. Results: Sixty-four subjects were enrolled, and 54 completed the study. The geometric mean ratios and 90% CI for the maximum plasma concentration (C max ) and area under the curve from time zero to the last sampling time (AUC t ) were 1.0716 (1.0369,1.1074) and 1.0497 (1.0243,1.0757) for amlodipine, 1.0396 (0.9818,1.1009) and 1.0138 (0.9716,1.0578) for olmesartan, and 1.0257 (0.9433,1.1152) and 1.0043 (0.9453,1.0669) for rosuvastatin. Fourteen cases of adverse events occurred in 12 subjects. There was no statistically significant clinical difference between the formulation groups. Conclusion: The 90% CI of the primary PK parameters were within the acceptance bioequivalence criteria, which is ln (0.8) and ln (1.25). These results indicate that the FDC formulation and co-administration of amlodipine, olmesartan and rosuvastatin are pharmacokinetically bioequivalent and have similar safety profiles.

<p>Comparison of Pharmacokinetics of a Fixed-Dose Combination of Amlodipine/Losartan/Rosuvastatin with Concomitant Administration of Amlodipine/Losartan and Rosuvastatin in Healthy Volunteers</p>

“…The number of study population which was able to meet the bioequivalence criteria with a significance level of 0.05 and 90% power was statistically calculated based on the previous study in which the highest value of intra-individual CV of PK parameter among the three active drugs and one metabolite was for the C max of losartan, which was about 36.5%. 16 Of the 56 subjects who completed this study, the highest value of the intra-individual CV was 30.80% (C max of losartan). The number of participants enrolled in the study validates the bioequivalence between the two treatments.…”

“…Similar to other comparative studies of FDC formulations of CCBs, ARBs, and statins, GMRs of all primary pharmacokinetic parameters were close to 1. 15,16 Approximately 14% of EXP3174, an active metabolite of losartan with a half-life of around 6 to 9 h, is formed by CYP2C9 and CYP3A4, and it is 10-to 40-fold more potent than losartan. 17 In addition to the active drugs, the PK profile of EXP3174 was analyzed in this study.…”

A Prospective Randomized, Double-Blind, Multi-Center, Phase III Clinical Trial Evaluating the Efficacy and Safety of Olmesartan/Amlodipine plus Rosuvastatin Combination Treatment in Patients with Concomitant Hypertension and Dyslipidemia: A LEISURE Study

“…In addition to this combination, we added rosuvastatin as a separate pill. This triple combination as SPC provided good safety and efficacy data and pharmacokinetic profile [29].…”

Pharmacokinetics and Bioequivalence Evaluation of 2 Olmesartan Medoxomil and Amlodipine Besylate Fixed‐Dose Combination Tablets in Healthy Chinese Volunteers Under Fasting and Fed Conditions

“…Previous studies have shown no pharmacokinetic (PK) interaction between olmesartan and amlodipine. In the fixed‐dose combination, olmesartan and amlodipine have synergistic antihypertensive effects, which can be used for preliminary treatment of hypertension 8,12,13 . The brand‐named preparation made by Daiichi Sankyo Europe GmbH was widely used in 30 countries around the world.…”