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Population Pharmacokinetic Model and Optimal Sampling Strategies for Micafungin in Critically Ill Patients Diagnosed with Invasive Candidiasis.
Boonstra, J M; van der Elst, K C; Zijlstra, J G; van der Werf, T S; Alffenaar, J W C; Touw, D J.
Afiliación
  • Boonstra JM; University of Groningen, University Medical Center Groningengrid.4494.d, Department of Clinical Pharmacy and Pharmacology, Groningen, the Netherlands.
  • van der Elst KC; University of Groningen, University Medical Center Groningengrid.4494.d, Department of Clinical Pharmacy and Pharmacology, Groningen, the Netherlands.
  • Zijlstra JG; University of Groningen, University Medical Center Groningengrid.4494.d, Department of Critical Care, Groningen, the Netherlands.
  • van der Werf TS; University of Groningen, University Medical Center Groningengrid.4494.d, Department of Internal Medicine, Groningen, the Netherlands.
  • Alffenaar JWC; University of Groningen, University Medical Center Groningengrid.4494.d, Department of Pulmonary Diseases and Tuberculosis, Groningen, the Netherlands.
  • Touw DJ; The University of Sydney, Faculty of Medicine and Health, School of Pharmacy, Sydney, New South Wales, Australia.
Antimicrob Agents Chemother ; 66(12): e0111322, 2022 12 20.
Article en En | MEDLINE | ID: mdl-36377940
Candida bloodstream infections are associated with high attributable mortality, where early initiation of adequate antifungal therapy is important to increase survival in critically ill patients. The exposure variability of micafungin, a first-line agent used for the treatment of invasive candidiasis, in critically ill patients is significant, potentially resulting in underexposure in a substantial portion of these patients. The objective of this study was to develop a population pharmacokinetic model including appropriate sampling strategies for assessing micafungin drug exposure in critically ill patients to support adequate area under the concentration-time curve (AUC) determination. A two-compartment pharmacokinetic model was developed using data from intensive care unit (ICU) patients (n = 19), with the following parameters: total body clearance (CL), volume of distribution of the central compartment (V1), inter-compartmental clearance (CL12), and volume of distribution of the peripheral compartment (V2). The final model was evaluated with bootstrap analysis and the goodness-of-fit plots for the population and individual predicted micafungin plasma concentrations. Optimal sampling strategies (with sampling every hour, 24 h per day) were developed with 1- and 2-point sampling schemes. Final model parameters (±SD) were: CL = 1.03 (0.37) (L/h/1.85 m2), V1 = 0.17 (0.07) (L/kg LBMc), CL12 = 1.80 (4.07) (L/h/1.85 m2), and V2 = 0.12 (0.06) (L/kg LBMc). Sampling strategies with acceptable accuracy and precision were developed to determine the micafungin AUC. The developed model with optimal sampling procedures provides the opportunity to achieve quick optimization of the micafungin exposure from a single blood sample using Bayesian software and may be helpful in guiding early dose decision-making.
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Candidiasis Invasiva / Antifúngicos Tipo de estudio: Diagnostic_studies / Prognostic_studies Límite: Humans Idioma: En Revista: Antimicrob Agents Chemother Año: 2022 Tipo del documento: Article País de afiliación: Países Bajos Pais de publicación: Estados Unidos
Texto completo
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Candidiasis Invasiva / Antifúngicos Tipo de estudio: Diagnostic_studies / Prognostic_studies Límite: Humans Idioma: En Revista: Antimicrob Agents Chemother Año: 2022 Tipo del documento: Article País de afiliación: Países Bajos Pais de publicación: Estados Unidos