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Correlation of Antimicrobial Pharmacokinetic Parameters with Therapeutic Efficacy in an Animal Model
Abstract
Current antimicrobial dosing regimens are designed to maintain active drug levels for most of the dosing interval and are based on 40-y-old observations. With use of numerous multiple-dosing regimens in an animal model, this study is the first to successfully minimize the interdependence between pharmacokinetic parameters and thereby determine, by stepwise multivariate regression analysis, that the time that serum levels exceeded the minimum inhibitory concentration (MIC) was the most significant parameter determining efficacy for beta-lactams and erythromycin against various pathogens, whereas the log area under the curve was the major parameter for aminoglycosides. Optimal dosing intervals were no greater than the time that serum levels exceeded the MIC plus the duration of the postantibiotic effect. Careful application of these concepts should allow other investigators to use more optimally dosed regimens than those previously used in preclinical trials and to design studies to improve on current dosing regimens for humans.
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Citations
Cited by
Craig, W. A. (1998) · Clinical Infectious Diseases · doi:10.1086/516284 · Cited by 2,908
Self-citationRoberts, J. A., Abdul-Aziz, M. H., Lipman, J., Mouton, J. W., Vinks, A. A., Felton, T. W., Hope, W. W., Farkas, A., Neely, M. N., Schentag, J. J., et al. (2014) · The Lancet Infectious Diseases · doi:10.1016/s1473-3099(14)70036-2 · Cited by 1,046
Antimicrobial pharmacodynamics: critical interactions of 'bug and drug'
Drusano, G. L. (2004) · Nature Reviews Microbiology · doi:10.1038/nrmicro862 · Cited by 930
McKinnon, P. S., Paladino, J. A., & Schentag, J. J. (2008) · International Journal of Antimicrobial Agents · doi:10.1016/j.ijantimicag.2007.12.009 · Cited by 464
The pharmacokinetic–pharmacodynamic approach to a rational dosage regimen for antibiotics
Toutain, P. L., del Castillo, J. R. E., & Bousquet-Mélou, A. (2002) · Research in Veterinary Science · doi:10.1016/s0034-5288(02)00039-5 · Cited by 384
Metadata
- Authors
- Vogelman, B., Gudmundsson, S., Leggett, J., Turnidge, J., Ebert, S., & Craig, W. A.
- Venue
- The Journal of Infectious Diseases
- Publisher
- Oxford University Press (OUP)
- Published
- 1988-10
- Volume
- 158
- Issue
- 4
- Pages
- 831-847
- ISSN
- 0022-1899 (ISSN-L)
- 1537-6613
- OpenAlex
- W2166840599
- Cited by
- 720
- References
- 0
- FWCI
- 12.94
- Type
- journal article
- Language
- en
- Open access
- closed
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- CoChat. (2026). Citation check: Correlation of Antimicrobial Pharmacokinetic Parameters with Therapeutic Efficacy in an Animal Model. https://app.cochat.ai/papers/10.1093/infdis/158.4.831
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- Vogelman, B., Gudmundsson, S., Leggett, J., Turnidge, J., Ebert, S., & Craig, W. A. (1988). Correlation of Antimicrobial Pharmacokinetic Parameters with Therapeutic Efficacy in an Animal Model. The Journal of Infectious Diseases. https://doi.org/10.1093/infdis/158.4.831
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Contains information from the Semantic Scholar Academic Graph Datasets, made available under the ODC Attribution License (ODC-BY 1.0).
Semantic Scholar’s data is described in: Kinney, R., et al. (2023). The Semantic Scholar Open Data Platform. arXiv:2301.10140.
