A Review of the Clinical Pharmacokinetics and Pharmacodynamics of Isavuconazole

Invasive fungal infections are a major cause of morbidity and mortality, especially for immunocompromised patients. Treatment options are few and most are limited by safety and formulation concerns. Isavuconazole is a new triazole antifungal agent with official indications for the treatment of invas...

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Bibliographic Details
Published in:European journal of drug metabolism and pharmacokinetics 2018-06, Vol.43 (3), p.281-290
Main Author: Wilby, Kyle John
Format: Article
Language:English
Subjects:
Antifungal Agents - pharmacokinetics
Antifungal Agents - therapeutic use
Biological Availability
Biomedical and Life Sciences
Biomedicine
Drug Monitoring - methods
Human Physiology
Humans
Medical Biochemistry
Mucormycosis - drug therapy
Nitriles - pharmacokinetics
Nitriles - therapeutic use
Pharmaceutical Sciences/Technology
Pharmacology/Toxicology
Pharmacy
Pyridines - pharmacokinetics
Pyridines - therapeutic use
Review Article
Triazoles - pharmacokinetics
Triazoles - therapeutic use
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Summary:Invasive fungal infections are a major cause of morbidity and mortality, especially for immunocompromised patients. Treatment options are few and most are limited by safety and formulation concerns. Isavuconazole is a new triazole antifungal agent with official indications for the treatment of invasive fungal infections caused by Aspergillus and Mucormycosis . Its clinical efficacy has been proven in two landmark trials, SECURE and VITAL. This review aims to summarize and evaluate the published literature reporting clinical pharmacokinetic and pharmacodynamic outcome data of isavuconazole in humans. Data from healthy volunteers demonstrated high oral bioavailability, high hepatic metabolism, and an extended elimination half-life. Data from diseased patients confirmed these findings and also consistently demonstrated that regular dosing of isavuconazole results in achievement of concentrations and exposures that meet pharmacodynamic targets for therapeutic efficacy. Additionally, it was found that renal dysfunction, and mucositis do not majorly affect pharmacokinetic or pharmacodynamic outcomes yet further study is required for severe hepatic and gastric impairment. Future studies should further attempt to understand dose and concentration response relationships, investigate the role (if any) of therapeutic drug monitoring, and strive to optimize dosing in special populations.
ISSN:0378-7966
2107-0180
DOI:10.1007/s13318-017-0445-7