Rifabutin treatment methods, uses, and compositions

Inventors

Dale, Glenn E. • Lociuro, Sergio • Kemmer, Christian • Trebosc, Vincent • Gitzinger, Marc

Assignees

Bioversys AG

Abstract

The invention provides systems and methods for increased clinical efficacy of rifabutin against A. baumannii. The invention takes advantage of the discovery of a ferric-coprogen (FhuE) receptor that is responsible for the uptake of rifabutin into A. baumannii cells. Methods preferably include obtaining a sample from a patient suspected of having an infection; performing a test on the sample to identify an infection of A. baumannii in the patient; and providing a formulation of rifabutin for treating the patient that, when administered to the patient, maximizes a resultant AUC and/or Cmax. The method may include administering the formulation of rifabutin to the patient. Preferably the formulation is delivered to the patient, e.g., by intravenous injection and results in a Cmax is that greater than about 2 mg/L and optionally less than about 50 mg/L.

Core Innovation

The patent describes treatment of Acinetobacter baumannii infection by administering a composition comprising an aqueous solution of rifabutin at a dose sufficient for activation of a ferric-coprogen (FhuE) receptor of A. baumannii cells. The activated FhuE receptor facilitates entry of rifabutin into A. baumannii cells, and the approach is framed around the ferric-coprogen (FhuE) receptor being a TonB-dependent siderophore receptor.

The patent emphasizes achieving systemic rifabutin exposures that support antibacterial activity, focusing on Cmax and AUC. It indicates that higher systemic rifabutin exposure is preferred and links dose-fractionation to the importance of both Cmax and AUC for activity, preferably via intravenous administration.

The patent further describes rifabutin intravenous aqueous compositions intended to support activation of the FhuE receptor. It provides compositions in which rifabutin is dissolved using a solvent and an acid, and specifies a preferred solvent system that includes components such as DMI and surfactants or surfactant-like excipients, together with a solvent:water formulation context.

Claims Coverage

The independent claim covers a treatment method in which an aqueous rifabutin solution is administered to activate the ferric-coprogen (FhuE) receptor on A. baumannii cells to facilitate rifabutin entry. The dependent claims further define formulation components, solvent choices, solvent-to-rifabutin ratio, dosing parameters using pharmacokinetic targets (Cmax and AUC), and administration by inhalation.

The claim set centers on treatment of A. baumannii infection by administering an aqueous rifabutin solution to activate the ferric-coprogen (FhuE) receptor and facilitate rifabutin entry, with dependent features directed to formulation components, solvent selection, solvent-to-rifabutin ratio, pharmacokinetic dosing ranges, and inhalation administration.

Stated Advantages

Documented Applications