BV100 (rifabutin for infusion) is being developed as an intravenous formulation for treating serious or life-threatening infections due to carbapenem-resistant Acinetobacter baumannii in patients with limited treatment options. Phase 1 studies were conducted to characterize the pharmacokinetics (PK), safety, and tolerability of BV100 in healthy volunteers after single and multiple doses. Single-ascending and multiple-ascending dose studies were conducted in healthy subjects to establish the PK profile of BV100. Blood samples were assayed to determine plasma concentrations of rifabutin and the major metabolite 25-O-desacetyl-rifabutin and to determine PK parameters. Subjects were assessed for safety and tolerability. The PK profile of BV100 was generally dose-proportional in the single-ascending dose studies with a t1/2 of 7.9-56.1 h, and Tmax of 1.0-1.75 h and increasing exposure with dose. A q12h versus q24h dosing interval resulted in approximately a 1.5-fold to 2-fold greater exposure of rifabutin. The 25-O-desacetyl-rifabutin metabolite represented A. baumannii infections.CLINICAL TRIALSThis study is registered with ClinicalTrials.gov as NCT04636983 and NCT05087069.
Kemmer et al. (Mon,) studied this question.