Clinical use of ceftriaxone: a pharmacokinetic-pharmacodynamic perspective on the impact of minimum inhibitory concentration and serum protein binding

Clinical Pharmacokinetics
T R Perry, Jerome J Schentag

Abstract

Ceftriaxone is a third-generation cephalosporin that is used for a variety of infections such as meningitis, gonorrhoea and community-acquired pneumonia. The most important aspects of its pharmacokinetics include a long half-life, excellent tissue penetration and saturable (dose-dependent) serum protein binding of the drug. A pharmacodynamic analysis [total area under the concentration-time curve (AUC)/minimum inhibitory concentration (MIC)] was performed in several populations (healthy volunteers, children, the elderly, and patients with renal and hepatic impairment) against various bacterial species (Streptococcus pneumoniae, the Enterobacteriacieae, methicillin-susceptible Staphylococcus aureus, and Pseudomonas aeruginosa). AUC/MIC [area under the inhibitory time curve (AUIC)] was chosen as the pharmacodynamic parameter for this analysis since ceftriaxone is a time-dependent killer and high peak concentrations are not needed. In addition, there is a significant correlation between AUIC, time when concentration exceeds the MIC (t > MIC) and time to eradication. Total and free AUICs (assuming a free fraction = 10%) were calculated since it is highly protein bound. It was postulated that a free AUIC of at least 125 would be req...Continue Reading

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