A Review of the Clinical Pharmacokinetics and Pharmacodynamics of Isavuconazole

European Journal of Drug Metabolism and Pharmacokinetics
Kyle John Wilby

Abstract

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 con...Continue Reading

References

Jun 15, 2006·Journal of Medical Microbiology·D A EnochN M Brown
Aug 13, 2014·The Journal of Antimicrobial Chemotherapy·Bettina M Knoll
Apr 29, 2015·Expert Review of Clinical Pharmacology·Jason N MooreWalter K Kraft
Mar 13, 2016·The Lancet Infectious Diseases·Francisco M MartyUNKNOWN VITAL and FungiScope Mucormycosis Investigators
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Citations

Apr 19, 2018·European Journal of Clinical Pharmacology·Elena ArsièDario Cattaneo
Oct 5, 2018·European Journal of Drug Metabolism and Pharmacokinetics·Zorica JovićMarina Kostić
May 5, 2018·Clinical Pharmacokinetics·Matthew W McCarthyVidmantas Petraitis
Nov 21, 2018·Chemotherapy·Francesco MarchesiPierantonio Menna
Dec 20, 2021·Therapeutic Drug Monitoring·Benjamin KablyEliane M Billaud

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Methods Mentioned

BETA
gastric bypass
gastric

Software Mentioned

VITAL

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