Actually, determining a surrogate marker and endpoint for chemotherapeutic agents, including antimicrobials, have always been problematic. In contrast to other drug groups, antimicrobials have to act on site of action, which is greatly varied according to the targeted infection. Generally, AUC:MIC ratio is used in case of quinolones and macrolides, however, in case of B-lactams and aminoglycosides, other surrogate markers, time above MIC and Cmax:MIC ratio, are used. AUC is the area under the plasma concentration-time curve, but the question is: does plasma concentration truly reflect the concentration of antimicrobial at the infection site? For example, macrolides are known to be uptaken by lung tissue, therefore their concentration in the lung is many fold higher than of plasma. On the other hand, macrolides distribution to the interstitial fluid is known to be poor, therefore their concentration in tissues, other than of lung, is expected to be substantially lower than of plasma. Unless you are dealing with bacteremia, you do not know for sure how much concentration the pathogen is exposed to. Advanced techniques, such as microdialysis, sometime used to solve this problem. Also, the pharmacodynamics interaction between antimicrobial and pathogen is varied according to the nature of the pathogen whether it is Gm+ or Gm-, and even by time because of the development of resistance.

To calculate the AUC of an antimicrobial it is necessary to determine the compartment model of the drug (i.e. NCA, one compartment or two compartment etc.). Further the route of administration also affects the AUC because the method of calculation of AUC varies accordingly. I hope the attached chapter will satisfy your query

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