Pharmacology of Azole Antifungal Agents

Ashley, Elizabeth Dodds

doi:10.3109/9780849387869-13

Cited by 2 publications

(7 citation statements)

References 186 publications

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“…Pertinent PK data for caspofungin include a peak serum concentration of approximately 10 g/ml and a sustained concentration of Ͼ1 g/ml (total drug concentrations) throughout the dosing interval following a loading dose of 70 mg and a daily dosing regimen of 50 mg (8,16). The AUC is approximately 120 mg ⅐ h/liter (total drug concentration).…”

Section: Resultsmentioning

confidence: 99%

“…without bisecting any species group. While extensive PD target studies have not been undertaken with caspofungin, the PK of the drug (70-mg loading dose and 50-mg maintenance dose) would produce concentrations above 1 g/ml (total drug concentration) throughout the treatment period (8,16). The ability of caspofungin to successfully treat infections due to isolates for which the MIC is as high as 2 g/ml is strongly supported by the data from clinical trials, as shown in Table 5.…”

Section: Downloaded Frommentioning

confidence: 93%

“…The results of PK/PD studies for both anidulafungin and micafungin reveal a C max of approximately 10 g/ml and trough concentrations of 1 to 2 g/ml (8,16). Both agents exhibit concentration-dependent killing and a prolonged (12 to 24 h) postantifungal effect (19,20).…”

Section: Vol 46 2008 Mic Breakpoints For Echinocandins Against Candmentioning

confidence: 99%

“…Both agents exhibit concentration-dependent killing and a prolonged (12 to 24 h) postantifungal effect (19,20). The AUC (total drug concentration) for anidulafungin (200-mg loading dose and 100-mg maintenance dose) is 112 mg ⅐ h/liter, and that for micafungin (100-mg daily dose) is 126 mg ⅐ h/liter (8,16). More-extensive animal model PD target investigation has been undertaken with these echinocandins (2,3).…”

Section: Vol 46 2008 Mic Breakpoints For Echinocandins Against Candmentioning

confidence: 99%

“…Members of the echinocandin class of antifungal agents act by inhibition of the synthesis of 1,3-␤-D-glucan in the fungal cell wall (8,16). All three available echinocandins-anidulafungin, caspofungin, and micafungin-possess fungicidal activity against most species of Candida, including polyene-and azole-resistant species (9,14,33,48,59,65).…”

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confidence: 99%

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Correlation of MIC with Outcome for Candida Species Tested against Caspofungin, Anidulafungin, and Micafungin: Analysis and Proposal for Interpretive MIC Breakpoints

et al. 2008

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The CLSI Antifungal Subcommittee followed the M23-A2 "blueprint" to develop interpretive MIC breakpoints for anidulafungin, caspofungin, and micafungin against Candida species. MICs of <2 g/ml for all three echinocandins encompass 98.8 to 100% of all clinical isolates of Candida spp. without bisecting any species group and represent a concentration that is easily maintained throughout the dosing period. Data from phase III clinical trials demonstrate that the standard dosing regimens for each of these agents may be used to treat infections due to Candida spp. for which MICs are as high as 2 g/ml. An MIC predictive of resistance to these agents cannot be defined based on the data from clinical trials due to the paucity of isolates for which MICs exceed 2 g/ml. The clinical data set included only three isolates from patients treated with an echinocandin (caspofungin) for which the MICs were >2 g/ml (two C. parapsilosis isolates at 4 g/ml and one C. rugosa isolate at 8 g/ml). Based on these data, the CLSI subcommittee has decided to recommend a "susceptible only" breakpoint MIC of <2 g/ml due to the lack of echinocandin resistance in the population of Candida isolates thus far. Isolates for which MICs exceed 2 g/ml should be designated "nonsusceptible" (NS). For strains yielding results suggestive of an NS category, the organism identification and antimicrobial-susceptibility test results should be confirmed. Subsequently, the isolates should be submitted to a reference laboratory that will confirm the results by using a CLSI reference dilution method.

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Section: Resultsmentioning

confidence: 99%

Section: Downloaded Frommentioning

confidence: 93%

Section: Vol 46 2008 Mic Breakpoints For Echinocandins Against Candmentioning

confidence: 99%

Section: Vol 46 2008 Mic Breakpoints For Echinocandins Against Candmentioning

confidence: 99%

mentioning

confidence: 99%

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Correlation of MIC with Outcome for Candida Species Tested against Caspofungin, Anidulafungin, and Micafungin: Analysis and Proposal for Interpretive MIC Breakpoints

et al. 2008

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Antifungal Drug Therapeutic Monitoring: What are the Issues?

Myers

Ashley

2015

Curr Clin Micro Rpt

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Therapeutic drug monitoring (TDM), an established practice for many antimicrobials, has recently seen increasing utilization in the management of patients receiving antifungal agents. There is a growing body of literature supporting the use of TDM for itraconazole, voriconazole, posaconazole, and flucytosine. In addition, clinical practice guidelines have been recently published that give recommendations on the appropriate use of TDM for antifungal agents. However, there are still uncertainties regarding the optimal use of antifungal TDM in clinical practice. We conducted a review of recent literature in order to describe the clinical situations and specific antifungal agents for which TDM is ideal and summarize key information about the pharmacokinetics, pharmacodynamics, drug toxicities, TDM concentration targets, and dose adjustment algorithms for antifungals in which routine TDM is performed.

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Pharmacology of Azole Antifungal Agents

Cited by 2 publications

References 186 publications

Correlation of MIC with Outcome for Candida Species Tested against Caspofungin, Anidulafungin, and Micafungin: Analysis and Proposal for Interpretive MIC Breakpoints

Correlation of MIC with Outcome for Candida Species Tested against Caspofungin, Anidulafungin, and Micafungin: Analysis and Proposal for Interpretive MIC Breakpoints

Antifungal Drug Therapeutic Monitoring: What are the Issues?

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