RESUMEN
We examine theoretically and experimentally the localized electrical modes existing in a bi-inductive electrical lattice containing a bulk or a surface capacitive impurity. By means of the formalism of lattice Green's functions, we are able to obtain closed-form expressions for the frequencies of the impurity (bound-state) eigenmodes and for their associated spatial profiles. This affords us a systematic understanding of how these mode properties change as a function of the system parameters. We test these analytical results against experimental measurements, in both the bulk and surface cases, and find very good agreement. Last, we turn to a series of quench experiments, where either a parameter of the lattice or the lattice geometry itself is rapidly switched between two values or configurations. In all cases, we are able to naturally explain the results of such quench experiments from the larger analytical picture that emerges as a result of the detailed characterization of the impurity-mode solution branches.
RESUMEN
PURPOSE: In patients with type 2 diabetes mellitus, fixed-dose combinations (FDCs) of antihyperglycemic medications may provide complementary efficacy while reducing tablet burden and improving compliance. The aim of this study was to assess the bioequivalence and tolerability of 2 FDCs of dapagliflozin and metformin extended-release (XR) versus their individual component (IC) tablets. METHODS: An open-label, balanced, randomized, 2-way crossover, 4-arm study was conducted in 129 healthy Brazilian subjects (aged 18-55 years). Two oral doses of the FDCs (5 mg dapagliflozin and 500 mg metformin XR, and 10 mg dapagliflozin and 1000 mg metformin XR) were evaluated in fed and fasted states. FINDINGS: Under fed and fasted conditions the 5 mg dapagliflozin and 500 mg metformin XR FDC showed bioequivalence to its ICs. The 10 mg dapagliflozin and 1000 mg metformin XR FDC was bioequivalent to its ICs in fed subjects. Although AUC for the 10 mg dapagliflozin and 1000 mg metformin XR FDC was bioequivalent in fasted subjects, the Cmax for metformin was not bioequivalent to its ICs in fasted subjects (upper 90% CI was 127.5%, and thus outside the 80%-125% bioequivalence interval). The small increase in the fasted state is not considered clinically meaningful due to the small magnitude of the difference (9.2%), the lack of metformin Cmax being associated with efficacy or tolerability concerns, and the fasted state not being the recommended state for dosing of metformin XR. The safety profile and tolerability of the FDCs were similar to those of their ICs and no deaths or serious adverse events were reported. IMPLICATIONS: Both FDCs of dapagliflozin and metformin XR were bioequivalent to their ICs in fed and fasted subjects, except for the metformin Cmax from the 10 mg dapagliflozin and 1000 mg metformin XR FDC in fasted subjects. These data support the use of a dapagliflozin and metformin XR FDC in patients with type 2 diabetes mellitus.