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Pharmacokinetic And Pharmacodynamic Studies Of A Novel Spectinamide Series Of Antituberculosis Agents, V. N. R. Pavan Kumar Vaddady
Pharmacokinetic And Pharmacodynamic Studies Of A Novel Spectinamide Series Of Antituberculosis Agents, V. N. R. Pavan Kumar Vaddady
Theses and Dissertations (ETD)
Spectinamides are novel amide derivatives of the antibiotic spectinomycin that have emerged as a new class of agents to treat tuberculosis. These agents showed potent in vitro activity against Mycobacterium tuberculosis (MTB) compared to spectinomycin and in a preliminary in vivo study in interferon gamma (IFN‑γ) knockout mice, spectinamide Lee1329 reduced the lung bacillary load of TB comparable to streptomycin. We hypothesized that the application of an iterative pharmacokinetics and pharmacodynamics (PK/PD) guided approach would facilitate the optimization of these lead compounds suitable for further development.
A series of in vitro experiments including parallel artificial membrane permeability assay (PAMPA), microsomal …