Comparison of the Fluoroquinolones Based on Pharmacokinetic...
Comparison of the Fluoroquinolones Based on Pharmacokinetic...
Assessment of pharmacodynamic activity from standard in vitro minimum inhibitory concentrations (MICs) alone is insufficient to predict in vivo potency. Achievable serum and tissue concentrations as well as pharmacokinetic characteristics must be considered. When pharmacokinetic and pharmacodynamic values are combined, the area under the inhibitory curve (AUIC) and peak concentration:MIC ratio predict clinical cure for fluoroquinolones. Clinical data and animal models indicate that a peak:MIC of 10:1 and above and an AUIC of 125 and above are predictive of a clinical cure for this class of antimicrobials against gram-negative organisms. The values may be used to compare and contrast fluoroquinolones to determine which would be best for treating a specific microorganism. Pharmacodynamic data also can be used to design regimens that minimize the risk of suboptimal drug levels. Ensuring the optimal fluoroquinolone dosage based on pharmacodynamic principles would diminish the emergence of resistant organisms and prevent treatment failures.
Several fluoroquinolones are marketed in the United States and numerous others are in development. It is important to compare and contrast the relative strengths, weaknesses, and distinguishing characteristics of the members of this expanding class of antimicrobials. Unfortunately, few clinical trials directly compare clinical efficacy and side effects of these agents. Although the minimum inhibitory concentration (MIC) is a useful predictor of the activity of an antimicrobial against a microorganism, it does not necessarily indicate relative in vivo potency. For example, two antibiotics with an MIC of 1.0 µg/ml should be evaluated quite differently if one has a peak concentration of 2 µg/ml and the other a peak of 20 µg/ml. Thus, pharmacokinetic parameters must be considered for proper assessment of a drug and dosage.
Pharmacodynamics study the relationship between drug concentration and pharmacologic effect. For antimicrobials, pharmacodynamic activity can be described as concentration dependent or time dependent. As fluoroquinolones have concentration-dependent killing, the peak:MIC and/or area under the curve in 24 hours (AUC24):MIC are pharmacodynamic values that best correlate with efficacy. Understanding these parameters can facilitate selection of effective antibiotics and optimal regimens to hasten response, prevent treatment failures, and minimize the development of resistance.
Assessment of pharmacodynamic activity from standard in vitro minimum inhibitory concentrations (MICs) alone is insufficient to predict in vivo potency. Achievable serum and tissue concentrations as well as pharmacokinetic characteristics must be considered. When pharmacokinetic and pharmacodynamic values are combined, the area under the inhibitory curve (AUIC) and peak concentration:MIC ratio predict clinical cure for fluoroquinolones. Clinical data and animal models indicate that a peak:MIC of 10:1 and above and an AUIC of 125 and above are predictive of a clinical cure for this class of antimicrobials against gram-negative organisms. The values may be used to compare and contrast fluoroquinolones to determine which would be best for treating a specific microorganism. Pharmacodynamic data also can be used to design regimens that minimize the risk of suboptimal drug levels. Ensuring the optimal fluoroquinolone dosage based on pharmacodynamic principles would diminish the emergence of resistant organisms and prevent treatment failures.
Several fluoroquinolones are marketed in the United States and numerous others are in development. It is important to compare and contrast the relative strengths, weaknesses, and distinguishing characteristics of the members of this expanding class of antimicrobials. Unfortunately, few clinical trials directly compare clinical efficacy and side effects of these agents. Although the minimum inhibitory concentration (MIC) is a useful predictor of the activity of an antimicrobial against a microorganism, it does not necessarily indicate relative in vivo potency. For example, two antibiotics with an MIC of 1.0 µg/ml should be evaluated quite differently if one has a peak concentration of 2 µg/ml and the other a peak of 20 µg/ml. Thus, pharmacokinetic parameters must be considered for proper assessment of a drug and dosage.
Pharmacodynamics study the relationship between drug concentration and pharmacologic effect. For antimicrobials, pharmacodynamic activity can be described as concentration dependent or time dependent. As fluoroquinolones have concentration-dependent killing, the peak:MIC and/or area under the curve in 24 hours (AUC24):MIC are pharmacodynamic values that best correlate with efficacy. Understanding these parameters can facilitate selection of effective antibiotics and optimal regimens to hasten response, prevent treatment failures, and minimize the development of resistance.
