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Population Pharmacokinetics of Isavuconazole in Adult: A Systematic Review

Na Chen1,2, Xiaojuan Wang1,2, Yinyan Li1,2

  • 1Department of Pharmaceutical, The First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, Zhejiang Province, People's Republic of China.

Infection and Drug Resistance
|December 13, 2023
PubMed

Insights

This review summarizes population pharmacokinetic models for isavuconazole (ISA), an antifungal drug. Findings support individualized dosing strategies for better patient outcomes in treating invasive fungal infections.

Area of Science:

  • Pharmacology and Pharmaceutical Sciences
  • Clinical Pharmacy and Therapeutics

Background:

  • Isavuconazole (ISA) is a vital second-generation triazole antifungal, uniquely approved as an oral formulation for invasive mucormycosis.
  • Population pharmacokinetic (PopPK) studies are increasingly reported for ISA, highlighting the need for a consolidated understanding.

Purpose of the Study:

  • To systematically review and summarize the characteristics of existing population pharmacokinetic models for isavuconazole in adult populations.
  • To provide a theoretical foundation for optimizing individualized isavuconazole administration strategies.

Main Methods:

  • Systematic literature search across major databases (PubMed, Embase, CNKI, Wanfang, VIP) for PopPK models of ISA published up to March 2023.
  • Inclusion of 6 studies encompassing diverse populations: healthy individuals, patients with malignant tumors/neutropenia, and solid organ transplant recipients.
  • Analysis of models employing two-compartment structures with first-order elimination and various oral absorption models (first-order and Weibull).

Main Results:

  • Body mass index (BMI) was the most frequently identified covariate influencing ISA pharmacokinetics, followed by body weight, lean body mass, race, sex, population type, and creatinine clearance.
  • Despite variations in covariates across studies, the estimated clearance rate (CL) of isavuconazole remained consistent among different populations.
  • Commonly studied dosing regimens included single doses of 40-400mg and multiple doses (200mg q8h for 48h, then 200mg qd).

Conclusions:

  • Existing population pharmacokinetic models for isavuconazole provide valuable insights into its disposition across various adult groups.
  • The identified covariates offer a basis for developing more precise, individualized dosing recommendations.
  • Future research should focus on external validation and expanding PopPK studies to special populations, including those with severe liver disease or on ECMO support.
Keywords:
covariatesisavuconazoleisavuconazonium sulfatepopulation pharmacokinetics

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