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Nonstationary Pharmacokinetics of Caspofungin in ICU Patients.
Borsuk-De Moor, Agnieszka; Sysiak-Slawecka, Justyna; Rypulak, Elzbieta; Borys, Michal; Piwowarczyk, Pawel; Raszewski, Grzegorz; Onichimowski, Dariusz; Czuczwar, Miroslaw; Wiczling, Pawel.
Afiliação
  • Borsuk-De Moor A; Department of Biopharmaceutics and Pharmacodynamics, Medical University of Gdansk, Gdansk, Poland.
  • Sysiak-Slawecka J; 2nd Department of Anaesthesiology and Intensive Therapy, Medical University of Lublin, Lublin, Poland.
  • Rypulak E; 2nd Department of Anaesthesiology and Intensive Therapy, Medical University of Lublin, Lublin, Poland.
  • Borys M; 2nd Department of Anaesthesiology and Intensive Therapy, Medical University of Lublin, Lublin, Poland.
  • Piwowarczyk P; 2nd Department of Anaesthesiology and Intensive Therapy, Medical University of Lublin, Lublin, Poland.
  • Raszewski G; Department of Physiopathology, Institute of Rural Health, Lublin, Poland.
  • Onichimowski D; Department of Anaesthesiology and Intensive Therapy, Faculty of Medicine, University of Warmia and Mazury, Olsztyn, Poland.
  • Czuczwar M; 2nd Department of Anaesthesiology and Intensive Therapy, Medical University of Lublin, Lublin, Poland.
  • Wiczling P; Department of Biopharmaceutics and Pharmacodynamics, Medical University of Gdansk, Gdansk, Poland wiczling@gumed.edu.pl.
Article em En | MEDLINE | ID: mdl-32601169
ABSTRACT
Standard dosing of caspofungin in critically ill patients has been reported to result in lower drug exposure, which can lead to subtherapeutic 24-h area under the curve to MIC (AUC0-24/MIC) ratios. The aim of the study was to investigate the population pharmacokinetics of caspofungin in a cohort of 30 intensive care unit patients with a suspected invasive fungal infection, with a large proportion of patients requiring extracorporeal therapies, including extracorporeal membrane oxygenation (ECMO) and continuous renal replacement therapy (CRRT). Caspofungin was administered as empirical 70 mg antifungal therapy administered intravenously (i.v.) on the first day and at 50 mg i.v. on the consecutive days once daily, and the concentrations were measured after three subsequent doses. Population pharmacokinetic data were analyzed by nonlinear mixed-effects modeling. The pharmacokinetics of caspofungin was described by two-compartment model. A particular drift of the individual clearance (CL) and the volume of distribution of the central compartment (V1) with time was discovered and described by including three separate typical values of CL and V1 in the final model. The typical CL values at days 1, 2, and 3 were 0.563 liters/h (6.7% relative standard error [6.7%RSE]), 0.737 liters/h (6.1%RSE), and 1.01 liters/h (9.1%RSE), respectively. The change in parameters with time was not explained by any of the recorded covariates. Increasing clearance with subsequent doses was associated with a clinically relevant decrease in caspofungin exposure (>20%). The use of ECMO, CRRT, albumin concentration, and other covariates did not significantly affect caspofungin pharmacokinetics. Additional pharmacokinetic studies are urgently required to assess the possible lack of acquiring steady-state and suboptimal concentrations of the drug in critically ill patients. (This study has been registered at ClinicalTrials.gov under identifier NCT03399032.).
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Texto completo: 1 Base de dados: MEDLINE Assunto principal: Infecções Fúngicas Invasivas / Antifúngicos Tipo de estudo: Prognostic_studies Limite: Humans Idioma: En Ano de publicação: 2020 Tipo de documento: Article

Texto completo: 1 Base de dados: MEDLINE Assunto principal: Infecções Fúngicas Invasivas / Antifúngicos Tipo de estudo: Prognostic_studies Limite: Humans Idioma: En Ano de publicação: 2020 Tipo de documento: Article