Pharmacokinetics and probability of target attainment for micafungin in normal-weight and morbidly obese adults
| Autor: | Roger J. M. Brüggemann, Eric P H van Dongen, Rob ter Heine, David M. Burger, René M J Wiezer, Roeland E Wasmann, Simon E. Koele, Catherijne A. J. Knibbe, Cornelis Smit |
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| Jazyk: | angličtina |
| Rok vydání: | 2019 |
| Předmět: |
Adult
Male 0301 basic medicine Microbiology (medical) medicine.medical_specialty Antifungal Agents Adolescent Echinocandin 030106 microbiology Population Microbial Sensitivity Tests Biostatistics Loading dose Plasma Young Adult 03 medical and health sciences 0302 clinical medicine Pharmacokinetics Internal medicine medicine Humans Pharmacology (medical) Obesity Prospective Studies 030212 general & internal medicine Dosing education Candida Pharmacology education.field_of_study Maintenance dose business.industry Micafungin Middle Aged Healthy Volunteers lnfectious Diseases and Global Health Radboud Institute for Health Sciences [Radboudumc 4] Infectious Diseases Pharmacodynamics Female business medicine.drug |
| Zdroj: | Journal of Antimicrobial Chemotherapy, 74, 978-985 Journal of Antimicrobial Chemotherapy Journal of Antimicrobial Chemotherapy, 74(4), 978-985 Journal of Antimicrobial Chemotherapy, 74, 4, pp. 978-985 |
| ISSN: | 0305-7453 |
| DOI: | 10.1093/jac/dky554 |
| Popis: | Contains fulltext : 202593.pdf (Publisher’s version ) (Closed access) OBJECTIVES: The rising pandemic of obesity means an increasing number of obese patients who require antimicrobial therapy for serious infections. Micafungin is an echinocandin drug frequently used as therapy or prophylaxis for fungal infections, predominantly with Candida species. In order to maximize the efficacy of micafungin in obese patients, the dose that corresponds to optimal exposure for each obese individual needs to be identified. METHODS: We performed a prospective study in 16 obese and 8 normal-weight healthy subjects with a weight ranging from 61.5-184 kg (ClinicalTrials.gov Identifier: NCT03102658). A population pharmacokinetic model was developed and used to simulate several dosing regimens to evaluate the PTA for relevant MICs to define the optimal dose using the pharmacokinetic/pharmacodynamic target of an AUC/MIC ratio above 5000. RESULTS: Total body weight was found to be most predictive for CL and V. Simulations showed that a 100 mg dose results in a PTA of >90% in patients weighing 125 kg infected with a Candida species with an MIC of 0.016 mg/L. For an MIC of 0.032 mg/L, a 300 mg maintenance dose is recommended above 125 kg weight. Furthermore, we demonstrate that patients can benefit from a loading dose (i.e. twice the maintenance dose). CONCLUSIONS: We present easy-to-use dose recommendations for obese patients, based on both weight and target MIC, that result in adequate exposure in patients with body weight up to 190 kg. |
| Databáze: | OpenAIRE |
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