Bibliographic Details
| Title: |
Isavuconazole Pharmacokinetics and Pharmacodynamics in Children. |
| Authors: |
Elhence, Hirsh1 (AUTHOR), Mongkolrattanothai, Kanokporn1,2 (AUTHOR), Mohandas, Sindhu1,2 (AUTHOR), Neely, Michael N.1,2,3 (AUTHOR) mneely@chla.usc.edu |
| Source: |
Pharmaceutics. Jan2023, Vol. 15 Issue 1, p75. 16p. |
| Subject Terms: |
*DRUG monitoring, *PHARMACODYNAMICS, *PHARMACOKINETICS, *DRUG dosage, *CHILD patients, *MYCOSES |
| Abstract: |
Isavuconazole is a broad-spectrum azole anti-fungal not yet approved in children. We conducted a retrospective, single-center review of isavuconazole use and routine therapeutic drug monitoring in pediatric patients, extracting demographic, dosing, concentration, mortality and hepatoxicity data. We constructed a nonparametric population model using Pmetrics. Of 26 patients, 19 (73%) were male. The mean (SD) age and weight were 12.7 (5.5) years and 50.9 (26.8) kg. Eighty percent received between 9.7 and 10.6 mg/kg per dose. Ten (38%) subjects had proven fungal disease and eight (31%) had probable disease, mostly with Candida and Aspergillus spp. The predicted steady-state isavuconazole concentrations in our patients were similar to previous reports in children and adults, and simulations with the proposed dosing of 10 mg/kg/dose every 8 h for 2 days followed by once daily maintenance matched effective adult exposures. Attributable mortality (5 of 11 deaths) was associated with steady-state daily AUC < 60 mg∗h/L and higher AST/ALT with trough concentrations > 5 mg/L. Neither dose nor trough alone correlated well with AUC, but AUC can be estimated with one sample 10 h after the first maintenance dose or a trough concentration, if combined with a Bayesian approach or a peak and trough without a Bayesian approach. [ABSTRACT FROM AUTHOR] |
|
Copyright of Pharmaceutics is the property of MDPI and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.) |
| Database: |
Academic Search Complete |
|
Full text is not displayed to guests. |
Login for full access.
|
