Impact of pharmacodynamics and pharmacokinetics on echinocandin dosing strategies.

OBJECTIVE

Studies of antibiotic pharmacokinetics and pharmacokinetic-pharmacodynamics are useful in the design of optimal dosing strategies. This review examines recent advances in echinocandin pharmacokinetics and pharmacodynamics, and discusses how these studies could lead to newer dosing strategies for the treatment of invasive candidiasis.

RESULTS

Recent population pharmacokinetic analyses of caspofungin and micafungin suggest that the patient's weight may affect the echinocandin serum drug concentrations achieved. This suggests that population pharmacokinetic studies in overweight and obese patients for all currently licensed echinocandins are needed. Pharmacokinetic-pharmacodynamic considerations suggest that high intermittent dosing of echinocandins may be desirable for the treatment of invasive candidiasis. For some agents such as micafungin, pharmacokinetic simulations have even identified human doses that could be used in these intermittent dosing schemes. These dosing strategies were subsequently found to be effective therapy in animal models. The potential limitations of high drug doses include a paradoxical decrease in microbial kill as well as the toxicity of high intermittent doses in patients. These will need to be addressed in clinical studies.

CONCLUSIONS

A better understanding of caspofungin, micafungin, and anidulafungin pharmacokinetic-pharmacodynamics will help in the design of new optimized dosing regimens for invasive candidiasis.