title: Clinical pharmacodynamic index identification for micafungin in esophageal candidiasis: dosing strategy optimization.
abstract: Echinocandins exhibit concentration-dependent effects on Candida species, and preclinical studies support the administration of large, infrequent doses. The current report examines the pharmacokinetics/pharmacodynamics of two multicenter, randomized trials of micafungin dosing regimens that differed in both dose level and dosing interval. Analysis demonstrates the clinical relevance of the dose level and area under the concentration-time curve (AUC). Better, although not statistically significant (P = 0.056), outcomes were seen with higher maximum concentrations of drug in serum (Cmax) and large, infrequent doses. The results support further clinical investigation of novel micafungin dosing regimens with large doses but less than daily administration. (These studies have been registered at ClinicalTrials.gov under registration no. NCT00666185 and NCT00665639.).
authors: Department of Medicine, University of Wisconsin, Madison, Wisconsin, USA.
authors: David R
authors: DR
authors: Andes
authors: Daniel K
authors: DK
authors: Reynolds
authors: Scott A
authors: SA
authors: Van Wart
authors: Alexander J
authors: AJ
authors: Lepak
authors: Laura L
authors: LL
authors: Kovanda
authors: Sujata M
authors: SM
authors: Bhavnani
mesh_terms: D000935:Antifungal Agents / Q000097:blood / Q000493:pharmacokinetics / Q000494:pharmacology*; D019540:Area Under Curve; D002175:Candida / Q000187:drug effects* / Q000254:growth & development; D002177:Candidiasis / Q000188:drug therapy* / Q000382:microbiology; D004305:Dose-Response Relationship, Drug; D004334:Drug Administration Schedule; D054714:Echinocandins / Q000097:blood / Q000493:pharmacokinetics / Q000494:pharmacology*; D004947:Esophagus; D006801:Humans; D055666:Lipopeptides / Q000097:blood / Q000493:pharmacokinetics / Q000494:pharmacology*; D000077551:Micafungin; D008826:Microbial Sensitivity Tests; D016896:Treatment Outcome
chemical_list: D000935:Antifungal Agents; D054714:Echinocandins; D055666:Lipopeptides; D000077551:Micafungin
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