Population pharmacokinetics/pharmacodynamics of micafungin against Candida species in obese, critically ill, and morbidly obese critically ill patients
| Autor: | Sonia Luque, Jason A. Roberts, Emilio Maseda, Santiago Grau, Alejandro Suarez-de-la-Rica, Ana Montero-Feijoo, Patricia Salgado, Maria-Pilar Castillo-Mafla, Carlos A García-Bernedo, Fernando Gilsanz, María-José Giménez |
|---|---|
| Rok vydání: | 2018 |
| Předmět: |
Male
0301 basic medicine Letter Antifungal Agents Critical Care and Intensive Care Medicine Body Mass Index law.invention Morbid obesity Echinocandins law Candida spp Candida Aged 80 and over 2. Zero hunger Candidiasis Area under the curve lcsh:Medical emergencies. Critical care. Intensive care. First aid Middle Aged Intensive care unit Obesity Morbid 3. Good health Area Under Curve Obesitat Female Monte Carlo Method medicine.drug Adult medicine.medical_specialty Critical Illness 030106 microbiology Microbial Sensitivity Tests Monte-Carlo simulation Lipopeptides 03 medical and health sciences Pharmacokinetics Internal medicine medicine Humans Obesity Dosing PK/PD models Aged Dose-Response Relationship Drug business.industry Research Micafungin PK/PD lcsh:RC86-88.9 ROC Curve Spain Pharmacodynamics business Body mass index |
| Zdroj: | Dipòsit Digital de Documents de la UAB Universitat Autònoma de Barcelona Critical Care, Vol 22, Iss 1, Pp 1-9 (2018) Critical Care Repositorio Institucional de la Consejería de Sanidad de la Comunidad de Madrid Consejería de Sanidad de la Comunidad de Madrid |
| Popis: | Altres ajuts: This work was supported in part by an unrestricted grant from Astellas Pharma S.A. (Madrid, Spain). The funder had no role in the study design, data collection and interpretation, or the decision to submit the work for publication. JAR is funded by a Career Development Fellowship from the National Health and Medical Research Council of Australia (APP1048652). Dosing in obese critically ill patients is challenging due to pathophysiological changes derived from obesity and/or critical illness, and it remains fully unexplored. This study estimated the micafungin probability of reaching adequate 24-h area under the curve (AUC)/minimum inhibitory concentration (MIC) values against Candida spp. for an obese/nonobese, critically ill/noncritically ill, large population. Blood samples for pharmacokinetic analyses were collected from 10 critically ill nonobese patients, 10 noncritically ill obese patients, and 11 critically ill morbidly obese patients under empirical/directed micafungin treatment. Patients received once daily 100-150 mg micafungin at the discretion of the treating physician following the prescribing information and hospital guidelines. Total micafungin concentrations were determined by high-performance liquid chromatography (HPLC). Monte-Carlo simulations were performed and the probability of target attainment (PTA) was calculated using the AUC/MIC cut-offs 285 (C. parapsilosis), 3000 (all Candida spp.), and 5000 (non parapsilosis Candida spp.). Intravenous once-daily 100-mg, 150-mg, and 200-mg doses were simulated at different body weights (45, 80, 115, 150, and 185 kg) and age (30, 50, 70 and 90 years old). PTAs ≥ 90% were considered optimal. Fractional target attainment (FTA) was calculated using published MIC distributions. A dosing regimen was considered successful if the FTA was ≥ 90%. Overall, 100 mg of micafungin was once-daily administered for nonobese and obese patients with body mass index (BMI) ≤ 45 kg/m 2 and 150 mg for morbidly obese patients with BMI > 45 kg/m 2 (except two noncritically ill obese patients with BMI ~ 35 kg/m 2 receiving 150 mg, and one critically ill patient with BMI > 45 kg/m 2 receiving 100 mg). Micafungin concentrations in plasma were best described using a two-compartment model. Weight and age (but not severity score) were significant covariates and improved the model. FTAs > 90% were obtained against C. albicans with the 200 mg/24 h dose for all body weights (up to 185 kg), and with the 150 mg/24 h for body weights < 115 kg, and against C. glabrata with the 200 mg/24 h dose for body weights < 115 kg. The lack of adequacy for the 100 mg/24 h dose suggested the need to increase the dose to 150 mg/24 h for C. albicans infections. Further pharmacokinetic/pharmacodynamic studies should address optimization of micafungin dosing for nonalbicans Candida infections. |
| Databáze: | OpenAIRE |
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