{"doi":"10.3390/jof9020211","title":"Population Pharmacokinetics of Isavuconazole in Critical Care Patients with COVID-19-Associated Pulmonary Aspergillosis and Monte Carlo Simulations of High Off-Label Doses","abstract":"<jats:p>Isavuconazole is a triazole antifungal agent recently recommended as first-line therapy for invasive pulmonary aspergillosis. With the COVID-19 pandemic, cases of COVID-19-associated pulmonary aspergillosis (CAPA) have been described with a prevalence ranging from 5 to 30%. We developed and validated a population pharmacokinetic (PKpop) model of isavuconazole plasma concentrations in intensive care unit patients with CAPA. Nonlinear mixed-effect modeling Monolix software were used for PK analysis of 65 plasma trough concentrations from 18 patients. PK parameters were best estimated with a one-compartment model. The mean of ISA plasma concentrations was 1.87 [1.29–2.25] mg/L despite prolonged loading dose (72 h for one-third) and a mean maintenance dose of 300 mg per day. Pharmacokinetics (PK) modeling showed that renal replacement therapy (RRT) was significantly associated with under exposure, explaining a part of clearance variability. The Monte Carlo simulations suggested that the recommended dosing regimen did not achieve the trough target of 2 mg/L in a timely manner (72 h). This is the first isavuconazole PKpop model developed for CAPA critical care patients underlying the need of therapeutic drug monitoring, especially for patients under RRT.</jats:p>","journal":"Journal of Fungi","year":2023,"id":654818,"datarank":0.5416376868966337,"base_score":3.6109179126442243,"endowment":3.6109179126442243,"self_citation_contribution":0.5416376868966337,"citation_network_contribution":0.0,"self_endowment_contribution":0.5416376868966337,"citer_contribution":0.0,"corpus_percentile":null,"corpus_rank":null,"citation_count":36,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":null,"is_data_producer":false,"deposit_databanks":null,"is_oa":false,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":null,"fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":1709028,"name":"Philippe Corne","orcid":null,"position":1,"is_corresponding":false},{"id":1380888,"name":"Grégoire Pasquier","orcid":"0000-0002-9152-5149","position":2,"is_corresponding":false},{"id":1709030,"name":"Céline Konecki","orcid":"0000-0002-6214-1613","position":3,"is_corresponding":false},{"id":1709031,"name":"Meriem Sadek","orcid":null,"position":4,"is_corresponding":false},{"id":1709032,"name":"Clément Le Bihan","orcid":null,"position":5,"is_corresponding":false},{"id":850940,"name":"Kada Klouche","orcid":"0000-0003-1633-7700","position":6,"is_corresponding":false},{"id":364267,"name":"Olivier Mathieu","orcid":"0000-0001-5302-1102","position":7,"is_corresponding":false},{"id":1018213,"name":"Jacques Reynes","orcid":"0000-0002-5893-2789","position":8,"is_corresponding":false},{"id":1709033,"name":"Yoann Cazaubon","orcid":"0000-0003-1032-0879","position":9,"is_corresponding":false},{"id":1709027,"name":"Lucas Perez","orcid":null,"position":0,"is_corresponding":false}],"reference_count":0,"raw_metadata":{"has_enrichment":true,"resolved":true,"title":"Population Pharmacokinetics of Isavuconazole in Critical Care Patients with COVID-19-Associated Pulmonary Aspergillosis and Monte Carlo Simulations of High Off-Label Doses","abstract":"<jats:p>Isavuconazole is a triazole antifungal agent recently recommended as first-line therapy for invasive pulmonary aspergillosis. With the COVID-19 pandemic, cases of COVID-19-associated pulmonary aspergillosis (CAPA) have been described with a prevalence ranging from 5 to 30%. We developed and validated a population pharmacokinetic (PKpop) model of isavuconazole plasma concentrations in intensive care unit patients with CAPA. Nonlinear mixed-effect modeling Monolix software were used for PK analysis of 65 plasma trough concentrations from 18 patients. PK parameters were best estimated with a one-compartment model. The mean of ISA plasma concentrations was 1.87 [1.29–2.25] mg/L despite prolonged loading dose (72 h for one-third) and a mean maintenance dose of 300 mg per day. Pharmacokinetics (PK) modeling showed that renal replacement therapy (RRT) was significantly associated with under exposure, explaining a part of clearance variability. The Monte Carlo simulations suggested that the recommended dosing regimen did not achieve the trough target of 2 mg/L in a timely manner (72 h). This is the first isavuconazole PKpop model developed for CAPA critical care patients underlying the need of therapeutic drug monitoring, especially for patients under RRT.</jats:p>","is_dataset_classified":null,"base_score":3.6109179126442243,"endowment":3.6109179126442243,"datacite_reuse_total":0,"file_count":0,"downloads":0,"views":0,"has_version_chain":false,"is_dataset":false,"is_oa":false,"pmid":"36836325","pmcid":"PMC9960864","openalex_id":"https://openalex.org/W4319296621","authors":[],"funders":[],"total_grants":0,"fwci":6.0736,"citation_percentile":0.97405374,"influential_citations":0,"citation_trend":[{"year":2023,"count":7},{"year":2024,"count":11},{"year":2025,"count":14},{"year":2026,"count":4}],"oa_status":"gold","license":"cc-by","oa_locations":[{"url":"https://www.mdpi.com/2309-608X/9/2/211/pdf?version=1675676451","host_type":"journal"},{"url":"https://www.mdpi.com/2309-608X/9/2/211/pdf?version=1675676451","host_type":"publisher"},{"url":"https://www.mdpi.com/2309-608X/9/2/211/pdf","host_type":"publisher"},{"url":"https://doi.org/10.3390/jof9020211","host_type":"journal"},{"url":"https://pubmed.ncbi.nlm.nih.gov/36836325","host_type":"repository"},{"url":"https://hal.science/hal-04005976","host_type":"repository"},{"url":"https://www.ncbi.nlm.nih.gov/pmc/articles/9960864","host_type":"repository"},{"url":"https://hal.science/hal-04585719","host_type":"repository"},{"url":"https://doaj.org/article/9b407aebdd44433a89e3b957174584bd","host_type":"repository"},{"url":"https://hal.science/hal-04005976/document","host_type":"repository"},{"url":"https://pmc.ncbi.nlm.nih.gov/articles/PMC9960864/pdf/jof-09-00211.pdf","host_type":"repository"},{"url":"https://europepmc.org/articles/PMC9960864","host_type":"Europe_PMC"},{"url":"https://europepmc.org/articles/PMC9960864?pdf=render","host_type":"Europe_PMC"}],"fields_of_study":["Antifungal resistance and susceptibility","Antibiotics Pharmacokinetics and Efficacy","Pneumocystis jirovecii pneumonia detection and treatment"],"mesh_terms":[],"keywords":["Pharmacokinetics","Medicine","Dosing","Population","Intensive care unit","Regimen","Aspergillosis","Therapeutic drug monitoring","Internal medicine","Intensive care medicine","Pharmacology","Immunology","Renal Replacement Therapy","Population Pharmacokinetics","Capa","Isavuconazole","Covid-19"],"sdg_mappings":[{"sdg_number":0,"sdg_label":"Good health and well-being"}],"linked_datasets":[],"clinical_trials":[],"software_tools":[],"database_accessions":[],"source":"live","citation_network_status":"fetched"},"created_at":"2026-08-11T08:31:58.579484Z","pmid":null,"pmcid":null,"fwci":null,"citation_percentile":null,"influential_citations":0,"oa_status":null,"license":null,"views":0,"total_file_size_bytes":0,"version_count":0,"fair_f":null,"fair_a":null,"fair_i":null,"fair_r":null,"fair_zscore":null,"fair_rationale":null,"fair_model":null,"fair_agent_version":null,"fair_fulltext_source":null,"fair_has_llm":null,"fair_computed_at":null,"clinical_trials":[],"software_tools":[],"db_accessions":[],"linked_datasets":[],"topics":[]}