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No Dose Adjustment for Isavuconazole Based on Age or Sex
- Source :
- Antimicrobial Agents and Chemotherapy
- Publication Year :
- 2019
- Publisher :
- American Society for Microbiology, 2019.
-
Abstract
- 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).<br />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.)
- Subjects :
- Adult
Male
Antifungal Agents
Pyridines
Population
Physiology
Single oral dose
Young Adult
03 medical and health sciences
0302 clinical medicine
Pharmacokinetics
Dose adjustment
Nitriles
Confidence Intervals
medicine
sex
Humans
Pharmacology (medical)
030212 general & internal medicine
Adverse effect
education
Pharmacology
0303 health sciences
education.field_of_study
030306 microbiology
business.industry
isavuconazole
Triazoles
Isavuconazonium
Confidence interval
Infectious Diseases
age
Toxicity
Female
business
pharmacokinetics
medicine.drug
Subjects
Details
- ISSN :
- 10986596 and 00664804
- Volume :
- 63
- Database :
- OpenAIRE
- Journal :
- Antimicrobial Agents and Chemotherapy
- Accession number :
- edsair.doi.dedup.....e608685cf7c292f0f34fb6502ef3dd8d