Pharmacokinetic investigations of isavuconazole in paediatric cancer patients show reduced exposure of isavuconazole after opening capsules for administration via a nasogastric tube
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| Název: | Pharmacokinetic investigations of isavuconazole in paediatric cancer patients show reduced exposure of isavuconazole after opening capsules for administration via a nasogastric tube |
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| Autoři: | Didi Bury, Tom F W Wolfs, Rob ter Heine, Eline W Muilwijk, Kim C M van der Elst, Wim J E Tissing, Roger J M Brüggemann |
| Přispěvatelé: | Infectiezieken, Infectieziekten patientenzorg, Child Health, Infection & Immunity, Apotheek Klinische Farmacie, PMC Medisch specialisten |
| Zdroj: | Journal of Antimicrobial Chemotherapy, 78, 12, pp. 2886-2889 |
| Informace o vydavateli: | Oxford University Press (OUP), 2023. |
| Rok vydání: | 2023 |
| Témata: | Adult, Radboudumc 9: Rare cancers Clinical Pharmacy, pediatrics, Adolescent, Pyridines, adult, isavuconazole, Radboud University Medical Center, Observational Study, Infant, 3. Good health, biological availability, Child, Preschool, Neoplasms, Nitriles, Journal Article, childhood cancer, Humans, Radboudumc 4: lnfectious Diseases and Global Health Clinical Pharmacy, Prospective Studies, nasogastric tube, Child, pharmacokinetics |
| Popis: | Objectives To study the isavuconazole pharmacokinetics in a real-life paediatric cohort and confirm whether the isavuconazole exposures are within the adult exposure range. Furthermore, we are the first to describe unbound isavuconazole pharmacokinetics. Methods In this prospective, observational study, the isavuconazole dosing regimen was as follows (IV/oral/nasogastric tube): 5.4 mg/kg isavuconazole (maximum 200 mg/dose) three times daily on Days 1 and 2, followed by 5.4 mg/kg isavuconazole (maximum 200 mg/dose) once daily. At least one pharmacokinetic curve was assessed. Non-linear mixed effects modelling was used for analysis. Monte Carlo simulations were performed with the above mentioned maintenance dose for IV administrations and a weight band dosing regimen for oral/nasogastric tube administrations: I) 37 kg (200 mg daily). Results Seventeen paediatric patients with a median age of 9 years (range 1–17) and median weight of 26.0 kg (range 8.4–78.5) were evaluated. A two-compartment model describing linear pharmacokinetics of the unbound concentrations and saturable protein binding fitted the isavuconazole concentrations best. The absolute bioavailability of isavuconazole was 41.0% (95% CI: 32.4%–50.8%). The median (IQR) simulated exposures (AUC0–24h, SS) of the total isavuconazole concentrations after IV and oral/nasogastric tube administration were 87.7 mg·h/L (70.5–105.1) and 50.3 mg·h/L (39.0–62.4), respectively. The unbound isavuconazole fraction (unbound/total) ranged from 0.5% to 2.3%. Conclusions This study revealed low bioavailability after nasogastric tube administration with opened capsules. Isavuconazole exposures were in the expected range following IV administration. Total and unbound isavuconazole pharmacokinetics were reported with a 5-fold range in the unbound fraction. |
| Druh dokumentu: | Article |
| Popis souboru: | application/pdf |
| Jazyk: | English |
| ISSN: | 1460-2091 0305-7453 |
| DOI: | 10.1093/jac/dkad324 |
| Přístupová URL adresa: | https://pubmed.ncbi.nlm.nih.gov/37864491 https://research.rug.nl/en/publications/1e67ff08-83e4-4935-9724-1ab970d17e97 https://doi.org/10.1093/jac/dkad324 https://hdl.handle.net/11370/1e67ff08-83e4-4935-9724-1ab970d17e97 https://dspace.library.uu.nl/handle/1874/451237 https://hdl.handle.net/2066/300234 |
| Rights: | OUP Standard Publication Reuse taverne |
| Přístupové číslo: | edsair.doi.dedup.....dee34a12b99e9387acc2047c062023ac |
| Databáze: | OpenAIRE |
Nájsť tento článok vo Web of Science | Abstrakt: | Objectives To study the isavuconazole pharmacokinetics in a real-life paediatric cohort and confirm whether the isavuconazole exposures are within the adult exposure range. Furthermore, we are the first to describe unbound isavuconazole pharmacokinetics. Methods In this prospective, observational study, the isavuconazole dosing regimen was as follows (IV/oral/nasogastric tube): 5.4 mg/kg isavuconazole (maximum 200 mg/dose) three times daily on Days 1 and 2, followed by 5.4 mg/kg isavuconazole (maximum 200 mg/dose) once daily. At least one pharmacokinetic curve was assessed. Non-linear mixed effects modelling was used for analysis. Monte Carlo simulations were performed with the above mentioned maintenance dose for IV administrations and a weight band dosing regimen for oral/nasogastric tube administrations: I) 37 kg (200 mg daily). Results Seventeen paediatric patients with a median age of 9 years (range 1–17) and median weight of 26.0 kg (range 8.4–78.5) were evaluated. A two-compartment model describing linear pharmacokinetics of the unbound concentrations and saturable protein binding fitted the isavuconazole concentrations best. The absolute bioavailability of isavuconazole was 41.0% (95% CI: 32.4%–50.8%). The median (IQR) simulated exposures (AUC0–24h, SS) of the total isavuconazole concentrations after IV and oral/nasogastric tube administration were 87.7 mg·h/L (70.5–105.1) and 50.3 mg·h/L (39.0–62.4), respectively. The unbound isavuconazole fraction (unbound/total) ranged from 0.5% to 2.3%. Conclusions This study revealed low bioavailability after nasogastric tube administration with opened capsules. Isavuconazole exposures were in the expected range following IV administration. Total and unbound isavuconazole pharmacokinetics were reported with a 5-fold range in the unbound fraction. |
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| ISSN: | 14602091 03057453 |
| DOI: | 10.1093/jac/dkad324 |