Pharmacokinetic Interaction Among Ezetimibe, Rosuvastatin, and Telmisartan.

To evaluate the pharmacokinetic interactions among rosuvastatin, ezetimibe, and telmisartan, a randomized, open-label, 3-period, 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 (Cmax,ss ), and the area under the time-concentration curve within a dosing interval at steady state (AUCtau,ss ) were estimated. Among the 36 randomized subjects, 31 subjects completed the study. The GMRs and 90%CIs of Cmax,ss and AUCtau,ss of total ezetimibe were not significantly altered. The Cmax,ss of free ezetimibe was increased (GMR, 1.85; 90%CI, 1.56-2.19) but not for the AUCtau,ss (GMR, 1.16; 90%CI, 1.06-1.26). Similarly, the Cmax,ss of rosuvastatin was increased (GMR, 2.13; 90%CI, 1.88-2.43) without a change in the AUCtau,ss (GMR, 1.09; 90%CI, 1.03-1.15). The Cmax,ss (GMR, 1.16; 90%CI, 1.01-1.32) and AUCtau,ss (GMR, 1.26; 90%CI, 1.17-1.37) of telmisartan were slightly increased. Considering the therapeutic range of the components, the interaction would have limited clinical impact.

Comparative Pharmacokinetics/Pharmacodynamics of Fixed-Dose Combination of Esomeprazole and Calcium Carbonate (AD-206) to the Conventional Esomeprazole.

PURPOSE: Proton pump inhibitors (PPIs) are used for the treatment of acid-related disorders. Demands for enhanced stability and faster onset led to the development of AD-206, a fixed-dose combination of a PPI (esomeprazole) with an antacid salt (calcium carbonate). This study compared the pharmacokinetics (PKs) and pharmacodynamics (PDs) of AD-206 (Addpharma) with conventional esomeprazole (Nexium®, AstraZeneca). MATERIALS AND METHODS: A randomized, open-label, two-treatment, two-sequence crossover study was conducted with 2 different doses of esomeprazole at 20 and 40 mg with a fixed calcium carbonate dose of 600 mg in AD-206. Forty-four subjects were included in each dose group and randomly received either AD-206 or the conventional esomeprazole for 7 consecutive days in each period. After a single- and multiple-dose, blood samples for the PK analysis were analyzed, and 24-hour intragastric pH monitoring was conducted. RESULTS: The systemic exposure of esomeprazole after a multiple-dose of AD-206 was similar to that of the conventional esomeprazole in both doses, but the time to reach the peak concentration was faster in AD-206. The percentage decrease from baseline in the integrated gastric acidity for a 24-hour interval after the dose was not significantly different between the AD-206 and the conventional esomeprazole after a single- and multiple-dose for both doses, and the time to reach pH 4 was faster for AD-206. CONCLUSION: AD-206 showed a similar systemic exposure and suppression of gastric acid secretion after a multiple-dose compared to the conventional esomeprazole.