Fluconazole dosing predictions in critically-ill patients receiving prolonged intermittent renal replacement therapy: a Monte Carlo simulation approach. Clin Nephrol 2016 Jul;86(7):43-50
Date
06/03/2016Pubmed ID
27251341DOI
10.5414/CN108824Scopus ID
2-s2.0-84983466300 (requires institutional sign-in at Scopus site) 16 CitationsAbstract
Fluconazole is a renally-eliminated antifungal commonly used to treat Candida species infections. In critically-ill patients receiving prolonged intermittent renal replacement therapy (PIRRT), limited pharmacokinetic (PK) data are available to guide fluconazole dosing. We used previously-published fluconazole clearance data and PK data of critically-ill patients with acute kidney injury to develop a PK model with the goal of determining a therapeutic dosing regimen for critically-ill patients receiving PIRRT. Monte Carlo simulations were performed to create a virtual cohort of patients receiving different fluconazole dosing regimens. Plasma drug concentration-time profiles were evaluated on the probability of attaining a mean 24-hour area under the drug concentration-time curve to minimum inhibitory concentration ratio (AUC24h : MIC) of 100 during the initial 48 hours of antifungal therapy. At the susceptibility breakpoint of Candida albicans (2 mg/L), 93 - 96% of simulated subjects receiving PIRRT attained the pharmacodynamic target with a fluconazole 800-mg loading dose plus 400 mg twice daily (q12h or pre and post PIRRT) regimen. Monte Carlo simulations of a PK model of PIRRT provided a basis for the development of an informed fluconazole dosing recommendation when PK data was limited. This finding should be validated in the clinical setting.
Author List
Gharibian KN, Mueller BAMESH terms used to index this publication - Major topics in bold
Acute Kidney InjuryAntifungal Agents
Area Under Curve
Candidiasis
Computer Simulation
Critical Illness
Fluconazole
Humans
Microbial Sensitivity Tests
Monte Carlo Method
Renal Replacement Therapy
Time Factors