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

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 (Cmax) and area under the curve from time zero to the last sampling time (AUCt) 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.

Effect from surface treatment of nickel-titanium rotary files on the fracture resistance.

This study was aimed to compare the cyclic fatigue resistance and torsional resistance of rotary instruments with and without surface treatment. G6 A2 (Group A2) with and G6 A2 without surface treatment after machining (Group AN) were compared in this study. ProTaper F2 (Group F2) which has similar dimension and shape was also used for comparison. To evaluate the torsional resistance, ultimate torsional strength and distortion angle until fracture were recorded, and the toughness was calculated. The cyclic fatigue resistance was compared by evaluating the number of cycles to failure in a simulated canal. Statistical analysis was performed by one-way analysis of variance and Tukey post hoc test (p = 0.05). After torsional and cyclic fatigue tests, all fracture fragments were observed under a scanning electron microscope. Group A2 showed higher cyclic fatigue resistance than the groups AN and F2 (p < 0.05). Although group A2 demonstrated lower ultimate torsional strength than the others, there were no significant differences in toughness among the groups. While obvious machining grooves were seen in groups AN and F2, group A2 showed smooth surface resulting from the surface treatment. The specimens of fracture fragments showed typical features of cyclic failure such as micro-cracks, overloaded fast fracture zone, and torsional fracture such as unwinding helix, circular abrasion marks and dimples. Under the conditions of this study, the surface treated instruments may improve cyclic fatigue resistance while maintaining the torsional resistances and mechanical properties.