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Comparative pharmacodynamics of garenoxacin, gemifloxacin, and moxifloxacin in community-acquired pneumonia caused by Streptococcus pneumoniae: a Monte Carlo simulation analysis.
Clin Ther. 2007 Dec; 29(12):2685-9.CT

Abstract

OBJECTIVE

This study used Monte Carlo simulations to assess the potential for attainment of pharmacodynamic targets with the fluoroquinolones garenoxacin, gemifloxacin, and moxifloxacin against Streptococcus pneumoniae in serum and epithelial lining fluid (ELF) from hospitalized patients with community-acquired pneumonia (CAP).

METHODS

Data on the free AUC over 24 hours (fAUC(0-24)), a measure of drug exposure, were derived from previously described population pharmacokinetic models for therapeutic doses of the 3 fluoroquinolones. MIC distribution data for S pneumoniae were obtained from the Canadian Respiratory Organism Susceptibility Study. These data were used to produce the ratio of fAUC(0-24) to the MIC(90) (fAUC(0-24)/MIC(90)), a pharmacodynamic predictor of bacterial eradication. Monte Carlo simulations were used to analyze the potential for garenoxacin 400 mg QD, gemifloxacin 320 mg QD, and moxifloxacin 400 mg QD to achieve target fAUC(0-24)/MIC(90) ratios of 30, 40, 100, and 120 against S pneumoniae in serum and ELF from hospitalized patients with CAP. Target ratios of 30 and 40 were used to assess the probability of bacterial eradication, while ratios of 100 and 120 were used to assess the probability of preventing development of resistance.

RESULTS

Monte Carlo simulations indicated that all 3 fluoroquinolones had a high probability (>90%) of attaining target fAUC(0-24)/MIC(90) ratios of 30 and 40 against S pneumoniae in both serum and ELF. Garenoxacin 400 mg QD was associated with a >95% probability of achieving target fAUC(0-24)/MIC(90) ratios of 100 and 120 in both serum and ELF. Both gemifloxacin 320 mg QD and moxifloxacin 400 mg QD were associated with high probabilities of attaining fAUC(0-24)/MIC(90) ratios of 100 and 120 in ELF (>95%); the probability of gemifloxacin and moxifloxacin attaining these targets in serum ranged from 78.3% to 88.0%.

CONCLUSION

Based on these simulations, garenoxacin 400 mg QD, gemifloxacin 320 mg QD, and moxifloxacin 400 mg QD appeared likely to achieve target serum and ELF concentrations against S pneumoniae in hospitalized patients with CAP, with a low potential to select for resistance.

Authors+Show Affiliations

Department of Pharmacy Practice and Pharmaceutical Sciences, College of Pharmacy, University of Minnesota, Duluth, Minnesota 55812, USA. noreddin@umn.eduNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Comparative Study
Journal Article

Language

eng

PubMed ID

18201584

Citation

Noreddin, Ayman M., et al. "Comparative Pharmacodynamics of Garenoxacin, Gemifloxacin, and Moxifloxacin in Community-acquired Pneumonia Caused By Streptococcus Pneumoniae: a Monte Carlo Simulation Analysis." Clinical Therapeutics, vol. 29, no. 12, 2007, pp. 2685-9.
Noreddin AM, Reese AA, Ostroski M, et al. Comparative pharmacodynamics of garenoxacin, gemifloxacin, and moxifloxacin in community-acquired pneumonia caused by Streptococcus pneumoniae: a Monte Carlo simulation analysis. Clin Ther. 2007;29(12):2685-9.
Noreddin, A. M., Reese, A. A., Ostroski, M., Hoban, D. J., & Zhanel, G. G. (2007). Comparative pharmacodynamics of garenoxacin, gemifloxacin, and moxifloxacin in community-acquired pneumonia caused by Streptococcus pneumoniae: a Monte Carlo simulation analysis. Clinical Therapeutics, 29(12), 2685-9. https://doi.org/10.1016/j.clinthera.2007.12.019
Noreddin AM, et al. Comparative Pharmacodynamics of Garenoxacin, Gemifloxacin, and Moxifloxacin in Community-acquired Pneumonia Caused By Streptococcus Pneumoniae: a Monte Carlo Simulation Analysis. Clin Ther. 2007;29(12):2685-9. PubMed PMID: 18201584.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Comparative pharmacodynamics of garenoxacin, gemifloxacin, and moxifloxacin in community-acquired pneumonia caused by Streptococcus pneumoniae: a Monte Carlo simulation analysis. AU - Noreddin,Ayman M, AU - Reese,Angela A, AU - Ostroski,Melissa, AU - Hoban,Daryl J, AU - Zhanel,George G, PY - 2007/10/02/accepted PY - 2008/1/19/pubmed PY - 2008/7/2/medline PY - 2008/1/19/entrez SP - 2685 EP - 9 JF - Clinical therapeutics JO - Clin Ther VL - 29 IS - 12 N2 - OBJECTIVE: This study used Monte Carlo simulations to assess the potential for attainment of pharmacodynamic targets with the fluoroquinolones garenoxacin, gemifloxacin, and moxifloxacin against Streptococcus pneumoniae in serum and epithelial lining fluid (ELF) from hospitalized patients with community-acquired pneumonia (CAP). METHODS: Data on the free AUC over 24 hours (fAUC(0-24)), a measure of drug exposure, were derived from previously described population pharmacokinetic models for therapeutic doses of the 3 fluoroquinolones. MIC distribution data for S pneumoniae were obtained from the Canadian Respiratory Organism Susceptibility Study. These data were used to produce the ratio of fAUC(0-24) to the MIC(90) (fAUC(0-24)/MIC(90)), a pharmacodynamic predictor of bacterial eradication. Monte Carlo simulations were used to analyze the potential for garenoxacin 400 mg QD, gemifloxacin 320 mg QD, and moxifloxacin 400 mg QD to achieve target fAUC(0-24)/MIC(90) ratios of 30, 40, 100, and 120 against S pneumoniae in serum and ELF from hospitalized patients with CAP. Target ratios of 30 and 40 were used to assess the probability of bacterial eradication, while ratios of 100 and 120 were used to assess the probability of preventing development of resistance. RESULTS: Monte Carlo simulations indicated that all 3 fluoroquinolones had a high probability (>90%) of attaining target fAUC(0-24)/MIC(90) ratios of 30 and 40 against S pneumoniae in both serum and ELF. Garenoxacin 400 mg QD was associated with a >95% probability of achieving target fAUC(0-24)/MIC(90) ratios of 100 and 120 in both serum and ELF. Both gemifloxacin 320 mg QD and moxifloxacin 400 mg QD were associated with high probabilities of attaining fAUC(0-24)/MIC(90) ratios of 100 and 120 in ELF (>95%); the probability of gemifloxacin and moxifloxacin attaining these targets in serum ranged from 78.3% to 88.0%. CONCLUSION: Based on these simulations, garenoxacin 400 mg QD, gemifloxacin 320 mg QD, and moxifloxacin 400 mg QD appeared likely to achieve target serum and ELF concentrations against S pneumoniae in hospitalized patients with CAP, with a low potential to select for resistance. SN - 0149-2918 UR - https://www.unboundmedicine.com/medline/citation/18201584/Comparative_pharmacodynamics_of_garenoxacin_gemifloxacin_and_moxifloxacin_in_community_acquired_pneumonia_caused_by_Streptococcus_pneumoniae:_a_Monte_Carlo_simulation_analysis_ L2 - https://linkinghub.elsevier.com/retrieve/pii/S0149-2918(07)00407-9 DB - PRIME DP - Unbound Medicine ER -