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No Dose Adjustment for Isavuconazole Based on Age or Sex

This phase 1, open-label, single-dose, parallel-group study evaluated the pharmacokinetics (PK) of isavuconazole after a single oral dose of the prodrug isavuconazonium sulfate in healthy nonelderly (age, 18 to 45 years) and elderly (age, ≥65 years) males and females. Overall, 48 subjects were enrol...

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Autores principales: Desai, Amit V., Han, David, Kowalski, Donna L., Lademacher, Christopher, Pearlman, Helene, Yamazaki, Takao
Formato: Online Artículo Texto
Lenguaje:English
Publicado: American Society for Microbiology 2019
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6535513/
https://www.ncbi.nlm.nih.gov/pubmed/30962330
http://dx.doi.org/10.1128/AAC.02629-18
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author Desai, Amit V.
Han, David
Kowalski, Donna L.
Lademacher, Christopher
Pearlman, Helene
Yamazaki, Takao
author_facet Desai, Amit V.
Han, David
Kowalski, Donna L.
Lademacher, Christopher
Pearlman, Helene
Yamazaki, Takao
author_sort Desai, Amit V.
collection PubMed
description This phase 1, open-label, single-dose, parallel-group study evaluated the pharmacokinetics (PK) of isavuconazole after a single oral dose of the prodrug isavuconazonium sulfate in healthy nonelderly (age, 18 to 45 years) and elderly (age, ≥65 years) males and females. Overall, 48 subjects were enrolled in the study (n = 12 each in groups of nonelderly males and females and elderly males and females). All subjects received a single oral dose of 372 mg of isavuconazonium sulfate (equivalent to 200 mg isavuconazole). PK samples were collected for analysis of isavuconazole plasma concentrations from the predose time point up to 336 h postdose. Data were analyzed using population pharmacokinetic (PPK) analysis. The resulting PPK model included two compartments with Weibull absorption function as well as interindividual variability with respect to clearance, intercompartment clearance, volumes of central and peripheral compartments, and two Weibull absorption parameters, RA and KAMAX. The PPK analysis showed that elderly females had the highest exposure versus males (ratio of total area under the time-concentration curve [AUC], 138; 90% confidence interval [CI], 118 to 161) and versus nonelderly females (ratio of AUC, 147; 90% CI, 123 to 176). Higher exposures in elderly females were not associated with significant toxicity or treatment-emergent adverse events, as measured in this study. No dose adjustments appear to be necessary based on either age group or sex even with an increase in exposure for elderly females. (This study has been registered at ClinicalTrials.gov under registration no. NCT01657890.)
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spelling pubmed-65355132019-06-03 No Dose Adjustment for Isavuconazole Based on Age or Sex Desai, Amit V. Han, David Kowalski, Donna L. Lademacher, Christopher Pearlman, Helene Yamazaki, Takao Antimicrob Agents Chemother Pharmacology This phase 1, open-label, single-dose, parallel-group study evaluated the pharmacokinetics (PK) of isavuconazole after a single oral dose of the prodrug isavuconazonium sulfate in healthy nonelderly (age, 18 to 45 years) and elderly (age, ≥65 years) males and females. Overall, 48 subjects were enrolled in the study (n = 12 each in groups of nonelderly males and females and elderly males and females). All subjects received a single oral dose of 372 mg of isavuconazonium sulfate (equivalent to 200 mg isavuconazole). PK samples were collected for analysis of isavuconazole plasma concentrations from the predose time point up to 336 h postdose. Data were analyzed using population pharmacokinetic (PPK) analysis. The resulting PPK model included two compartments with Weibull absorption function as well as interindividual variability with respect to clearance, intercompartment clearance, volumes of central and peripheral compartments, and two Weibull absorption parameters, RA and KAMAX. The PPK analysis showed that elderly females had the highest exposure versus males (ratio of total area under the time-concentration curve [AUC], 138; 90% confidence interval [CI], 118 to 161) and versus nonelderly females (ratio of AUC, 147; 90% CI, 123 to 176). Higher exposures in elderly females were not associated with significant toxicity or treatment-emergent adverse events, as measured in this study. No dose adjustments appear to be necessary based on either age group or sex even with an increase in exposure for elderly females. (This study has been registered at ClinicalTrials.gov under registration no. NCT01657890.) American Society for Microbiology 2019-05-23 /pmc/articles/PMC6535513/ /pubmed/30962330 http://dx.doi.org/10.1128/AAC.02629-18 Text en Copyright © 2019 Desai et al. https://creativecommons.org/licenses/by/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution 4.0 International license (https://creativecommons.org/licenses/by/4.0/) .
spellingShingle Pharmacology
Desai, Amit V.
Han, David
Kowalski, Donna L.
Lademacher, Christopher
Pearlman, Helene
Yamazaki, Takao
No Dose Adjustment for Isavuconazole Based on Age or Sex
title No Dose Adjustment for Isavuconazole Based on Age or Sex
title_full No Dose Adjustment for Isavuconazole Based on Age or Sex
title_fullStr No Dose Adjustment for Isavuconazole Based on Age or Sex
title_full_unstemmed No Dose Adjustment for Isavuconazole Based on Age or Sex
title_short No Dose Adjustment for Isavuconazole Based on Age or Sex
title_sort no dose adjustment for isavuconazole based on age or sex
topic Pharmacology
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6535513/
https://www.ncbi.nlm.nih.gov/pubmed/30962330
http://dx.doi.org/10.1128/AAC.02629-18
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