Model simulation of a single oral dose of cefuroxime axetil and the related in-vitro kill kinetics against four bacterial species

Silley, P.; Monsey, D.; Harris, Anne

doi:10.1093/jac/25.1.83

Cited by 9 publications

(2 citation statements)

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“…The antimicrobial effect of antibiotics administered by different modes may be better related to the AUC than to the drug concentration at any time (7). AUC analysis of the antimicrobial effect has been successfully applied to compare the efficacies of such treatments as short-and long-term infusions of sisomicin in an in vitro dynamic model (7,10), different dosing regimens of ampicillin (27), and use of cefuroxime against different bacteria (25) in addition to others. In the present study, the AUC analysis was used to compare bolus administration with continuous infusions of meropenem.…”

Section: Discussionmentioning

confidence: 99%

Relationships between antimicrobial effect and area under the concentration-time curve as a basis for comparison of modes of antibiotic administration: meropenem bolus injections versus continuous infusions

Firsov¹,

Mattie²

1997

Antimicrob Agents Chemother

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In comparative studies of different modes of administration (MAs) simulated in in vitro dynamic models, only one dose of antibiotic is usually mimicked. Such an experimental design can provide a prediction of the antimicrobial effect (AME) of a given combination of drug, clinical isolate, and infection site, but may be inappropriate for accurate comparison of MAs. An alternative design providing comparison of different MAs with various antibiotic doses in a wide range and with evaluation of the respective relationships between AME and the AUC was proposed and examined. Two series of meropenem pharmacokinetic profiles, i.e., monoexponentially decreasing concentrations (bolus doses) and constant concentrations (6-h continuous infusion), were in vitro simulated. The simulated initial concentrations (Co[from 0.62 to 48 micrograms/ml]) and steady-state concentrations (Css[from 0.016 to 8 micrograms/ml]) were chosen to provide similar AUC for 0 to 6 h (AUC0-6) ranges for both MAs (from 0.070 to 50.0 micrograms.h/ml and from 0.09 to 48.0 micrograms.h/ml, respectively). The AME of meropenem on Staphylococcus aureus ATCC 25923 (MIC, 0.06 micrograms/ml) was determined at each time (t) point as a difference (E) between the logarithms of viable counts (N) in the control cultures without antibiotic (NC) and in cultures exposed to antibiotics (NA). Time courses of E observed at different Co of Css levels were compared in terms of the areas under the E-t curves (ABBCt). The finite values of the ABBCt observed by the end of the 6 -h observation period, which are equivalent to the area between bacterial count-time curves observed in the absence and presence of antibiotic (ABBC), were plotted versus the respective AUCs produced by each of the MAs. The ABBC versus AUC curves had a similar pattern: a plateau achieved at high AUCs followed by a steep rise in ABBC at relatively low AUCs was inherent in both of the MAs. The superiority of bolus dosing over the infusions could be documented only for meropenem concentrations below the MIC. At higher Co or Css (i.e., at an AUC of > or = 0.4 micrograms.h/ml), the ABBC versus AUC curves plotted for each of the MAs could practically be superimposed. On the whole, both MAs appeared to be equiefficient in terms of the ABBC. These results suggest that AUC analysis of the AME may be a useful tool for comparing different MAs. Such comparative studies should be designed in a manner that provides the use of similar AUC ranges, since the AUC may be considered as a common pharmacokinetic denominator in comparing one MA or dosing regimen to another.

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Section: Discussionmentioning

confidence: 99%

Relationships between antimicrobial effect and area under the concentration-time curve as a basis for comparison of modes of antibiotic administration: meropenem bolus injections versus continuous infusions

Firsov¹,

Mattie²

1997

Antimicrob Agents Chemother

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“…[81][82][83] Similar comparisons with ␤-lactams revealed agreement between clinical trials 42,[84][85][86] and in vitro model studies. 10,27,28,30,43 Thus, in vitro models may successfully mimic in vivo studies and, therefore, serve as tractable systems for examining the fundamental biology that underlies drugpathogen interactions. Few studies have tried to compare in vivo and in vitro studies directly by standardizing and controlling, as thoroughly as possible, the conditions in the two types of approaches.…”

Section: Success Stories For In Vitro Pharmacodynamic Modelsmentioning

confidence: 99%

What In Vitro Models of Infection Can and Cannot Do

White

2001

Pharmacotherapy

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The science of pharmacodynamics analyzes the relationship between an antimicrobial's bactericidal effects and its pharmacokinetics. Ideally, randomized and well-controlled clinical trials are the best way to determine pharmacodynamic properties. However, in vitro models that recapitulate in vivo drug clearance profiles represent an increasingly important technology for carrying out pharmacodynamic studies in a more cost-effective, timely, and easily controlled fashion. Although in vitro pharmacodynamic models cannot incorporate all variables seen in vivo, they do provide valuable information for the drug development process and the determination of optimal dosing regimens.

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High-performance liquid chromatographic assay with electrochemical detection for azithromycin in serum and tissues

Shepard

Duthu

Ferraina

et al. 1991

Journal of Chromatography B: Biomedical Sciences and Applicatio

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Model simulation of a single oral dose of cefuroxime axetil and the related in-vitro kill kinetics against four bacterial species

Cited by 9 publications

References 0 publications

Relationships between antimicrobial effect and area under the concentration-time curve as a basis for comparison of modes of antibiotic administration: meropenem bolus injections versus continuous infusions

Relationships between antimicrobial effect and area under the concentration-time curve as a basis for comparison of modes of antibiotic administration: meropenem bolus injections versus continuous infusions

What In Vitro Models of Infection Can and Cannot Do

High-performance liquid chromatographic assay with electrochemical detection for azithromycin in serum and tissues

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