ArticleThe Journal of antimicrobial chemotherapy2026
The magnitude of the pharmacodynamic index for NOSO-502: pathogen clearance, emergence of resistance and human dose predictions.
Article in The Journal of antimicrobial chemotherapy, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.
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Abstract
backgroundNOSO-5O2 is the first clinical candidate of a new antimicrobial class, the odilorhabdins. The pharmacodynamics of NOSO-502 was studied to establish the magnitude of the pharmacodynamic index (PDI) and make human dose predictions.
methodsIn vitro experiments using different types of media were performed in time-kill curves and a pharmacokinetic model. In vivo experiments were conducted in the neutropenic murine thigh infection model. Six E. coli (MIC 1-8 mg/L) and two K. pneumoniae (MIC 1-2 mg/L) strains were used. 24 h bacteriostatic and 1- and 2-log10 kill effects were related to fAUC0-24/MIC and fAUC0-24/MIC per length of dosing interval (fAUC0-24/MIC·1/tau). Human pharmacokinetic parameters were predicted using interspecies allometric scaling and used to simulate the dose needed to reach the bacteriostatic PDI target for E. coli.
resultsThe in vitro activity of NOSO-502 was dependent on the media and the strength of Mueller-Hinton Broth II (MHBII) used such that fAUC0-24/MIC ratios were higher when measured in 100% MHBII than 50% MHBII. In vivo for E. coli, the fAUC0-24/MIC for bacteriostatic effect and 1-log10 reduction in bacterial count were 10.7 ± 10.9 and 18.2 ± 16.5, respectively. The final human predicted parameters of the model had CV values of <20%. The human dose required to achieve the bacteriostatic fAUC0-24/MIC for each E. coli strain varied from 149 to 1717 mg/day.
conclusionsA combination of the use of PDI targets and prediction of human pharmacokinetics allowed effective doses of NOSO-502 in man to be estimated.
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