Activity of AFN-1252, a novel FabI inhibitor, against Staphylococcus aureus in an in vitro pharmacodynamic model simulating human pharmacokinetics.

Abstract

AFN-1252, a potent enoyl-ACP reductase (FabI) inhibitor, is under development for the treatment of Staphylococcus aureus infections. The activity of AFN-1252 against two isolates of S. aureus, MSSA 26213 and MRSA S186, was studied in an in vitro pharmacodynamic model simulating AFN-1252 pharmacokinetics in man. Reductions in bacterial viable count over the first 6 hours were generally 1-2 logs and maximal reductions in viable count were generally achieved at fAUC/MIC ratios of 100-200. Maximum reductions in viable count against MSSA 29213 and MRSA S186 were approximately 4 logs, achieved by 450 mg q12h (fAUC/MIC = 1875) dosing at 28 hours. Staphylococcal resistance to AFN-1252 did not develop throughout the 48-hour experiments. As multidrug resistance continues to increase, these studies support the continued investigation of AFN-1252 as a targeted therapeutic for staphylococcal infections.

• Authors: Brian T Tsuji, Yoriko Harigaya, Alan J Lesse, Alan Forrest, Dung Ngo
• Journal: Journal of chemotherapy (Florence, Italy) (J Chemother) Vol. 25 Issue 1 Pg. 32-5 (Feb 2013) ISSN: 1973-9478 [Electronic] England
• PMID: 23433442 (Publication Type: Journal Article)

Chemical References

• API 1252
• Anti-Bacterial Agents
• Benzofurans
• Pyrones

Topics

• Anti-Bacterial Agents (pharmacokinetics, pharmacology)
• Benzofurans (pharmacokinetics, pharmacology)
• Humans
• Methicillin-Resistant Staphylococcus aureus (drug effects)
• Microbial Sensitivity Tests
• Models, Biological
• Pyrones (pharmacokinetics, pharmacology)
• Staphylococcal Infections (drug therapy, metabolism)
• Staphylococcus aureus (drug effects)