Using Pharmacokinetics in Drug Therapy VIII: Pharmacokinetic Evaluation of Antibiotic Dosage Regimens

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Abstract
The highest and lowest approved dosage regimens for 15 antibiotics were evaluated, using retrospective pharmacokinetic analysis of 65 published studies. The pharmacokinetic indices assessed were the three components of the steady-state temporal blood concentration profile (1) the magnitude of the peak blood level compared to the minimum inhibitory concentration (Cmax∞/MIC); (2) the duration of the blood level above the MIC during each dosage interval (hours supra-MIC/Τ); and (3) the product of 1 and 2 (the intensity factor). In considering the highest approved dosage regimens for treating very susceptible microorganisms, there was more than a 75-fold, 5-fold and 300-fold variation in the various antibiotics for Cmax∞/MIC, hours supra-MIC/Τ, and the intensity factor, respectively. This suggests that some antibiotics may be be effective at lower doses than commonly used, while others may need to be used more aggressively. Considering the pharmacokinetic indices and antibiotics studied, tetracycline, amikacin, cefazolin, ampicillin, and vancomycin demonstrate the best pharmacokinetic performance for the tetracycline, aminoglycoside, cephalosporin, penicillin, and miscellaneous groups, respectively. Antibiotics whose protein binding is 80% or greater showed substantially reduced performance in the pharmacokinetic indices evaluated. Of the three pharmacokinetic indices, Cmax∞/MIC appeared to provide the best contribution to successful dosage regimens.

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