Total bodyweight and sex both drive pharmacokinetic variability of fluconazole in obese adults
| Autor: | Lu Chen, Koen P van Rhee, Roeland E Wasmann, Elke H J Krekels, Marinus J Wiezer, Eric P A van Dongen, Paul E Verweij, Paul D van der Linden, Roger J Brüggemann, Catherijne A J Knibbe |
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| Rok vydání: | 2022 |
| Předmět: |
Pharmacology
Microbiology (medical) Adult Male Body Weight lnfectious Diseases and Global Health Radboud Institute for Molecular Life Sciences [Radboudumc 4] Infectious Diseases lnfectious Diseases and Global Health Radboud Institute for Health Sciences [Radboudumc 4] Mycoses Humans Pharmacology (medical) Female Obesity Prospective Studies Fluconazole |
| Zdroj: | Journal of Antimicrobial Chemotherapy, 77, 8, pp. 2217-2226 Journal of Antimicrobial Chemotherapy, 77(8), 2217-2226. OXFORD UNIV PRESS Journal of Antimicrobial Chemotherapy, 77, 2217-2226 |
| ISSN: | 0305-7453 |
| DOI: | 10.1093/jac/dkac160 |
| Popis: | Background Fluconazole is commonly used to treat or prevent fungal infections. It is typically used orally but in critical situations, IV administration is needed. Obesity may influence the pharmacokinetics and therapeutic efficacy of a drug. In this study, we aim to assess the impact of obesity on fluconazole pharmacokinetics given orally or IV to guide dose adjustments for the obese population. Methods We performed a prospective pharmacokinetic study with intensive sampling in obese subjects undergoing bariatric surgery (n = 17, BMI ≥ 35 kg/m2) and non-obese healthy controls (n = 8, 18.5 ≤ BMI Results A total of 421 fluconazole concentrations in 25 participants (total bodyweight 61.0–174 kg) until 48 h after dosing were obtained. An estimated bioavailability of 87.5% was found for both obese and non-obese subjects, with a 95% distribution interval of 43.9%–98.4%. With increasing total bodyweight, both higher CL and Vd were found. Sex also significantly impacted Vd, being 27% larger in male compared with female participants. Conclusions In our population of obese but otherwise healthy individuals, obesity clearly alters the pharmacokinetics of fluconazole, which puts severely obese adults, particularly if male, at risk of suboptimal exposure, for which adjusted doses are proposed. |
| Databáze: | OpenAIRE |
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