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, 18 (4), 317-321

Isavuconazole Kinetic Exploration for Clinical Practice

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Isavuconazole Kinetic Exploration for Clinical Practice

Léa Darnaud et al. Drugs R D.

Abstract

Background: Isavuconazole is a new antifungal prodrug for the treatment of invasive aspergillosis and mucormycosis. As no clear pharmacokinetic-pharmacodynamic relationship has been established for patients, therapeutic drug monitoring is not currently required. However, as isavuconazole is a new drug, clinicians are sometimes sceptical about the exposure achieved in their patients and seek pharmacokinetic exploration. A minimal response consists of determining that the patient's pharmacokinetic profile agrees with profiles reported by Desai et al. using concentrations from the SECURE study.

Methods: Based on one concentration and Desai et al.'s population-pharmacokinetic model, it is possible to estimate a patient's most likely pharmacokinetic profile. If a patient's pharmacokinetic profile is close to the profiles reported by Desai et al., therapeutic drug monitoring is not required. In contrast, when the pharmacokinetic profile differs from the Desai et al. profiles, isavuconazole concentration monitoring and pharmacokinetic profile modeling are the only methods for obtaining information on a patient's exposure and the efficacy of isavuconazole.

Results: Four patients presented with surprising pharmacokinetic profiles, unexplained by drug interactions or cytochrome P450 3A4/5 polymorphisms. For two of them, a drug dosage adjustment was proposed and applied by clinicians, together with a check for a new pharmacokinetic profile a few days later.

Conclusions: Collecting one blood sample just before the first maintenance dose to make an early estimation of the patient's most likely pharmacokinetic profile is one method of identifying patients with outlier pharmacokinetic behavior.

Conflict of interest statement

All authors have no conflicts of interest that are directly relevant to the contents of this article.

Figures

Fig. 1
Fig. 1
Patients 1–4: kinetic profile of isavuconazole. The white curve shows the median kinetic profile. “Extremes” profiles were found in less than 5% and greater than 95% of the population (black curves). The red curve shows the estimated kinetic profile of the patient. The black stars represent the measured concentrations while the green stars represent the estimated trough concentrations in the case of individualized dosage adjustment. Therapeutic drug monitoring confirmed the estimated values. Cestimated, estimated concentration using Desai's POP PK model, Cmax maximum plasma concentration, Cmeasured, measured concentration from the patient's blood sample D day

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