Individualized Precision Isavuconazole Therapy Guided by PK/PD Principles for the Geriatric Population

Обзор

Esconazole, as a novel triazole antifungal drug, has broad-spectrum antifungal activity, good tissue penetration and low toxicity risk. It has been recommended by domestic and international guidelines as a first-line treatment for invasive fungal infections. Due to its good pharmacokinetic properties and the lack of evidence to associate plasma concentration with efficacy and toxicity, therapeutic drug monitoring is not routinely recommended at present. However, the pharmacokinetic characteristics of isaconazole have not been fully clarified in special populations, especially elderly patients. Elderly patients often have multiple organ function declines (such as liver function damage and renal insufficiency), and need to use multiple drugs in combination for a long time. This may affect the activity of drug-metabolizing enzymes or the plasma protein binding rate to change their clearance ability, leading to further amplification of individual differences in blood drug concentrations. Based on this, this study intends to focus on elderly patients with invasive fungal infections and systematically explore the optimal administration regimen of esconazole. By systematically analyzing the current changes in blood drug concentration at different administration doses during treatment, as well as the related drug toxicity reactions and therapeutic effects, the independent influencing factors of dose adjustment were identified. The differences in efficacy and safety between individualized dose reduction regimens and standard regimens were compared to provide a basis for the precise treatment of isaconazole in elderly patients.

Вмешательства

• Диагностический тест Liquid chromatography-tandem mass spectrometry
  Blood samples were collected at different time points for drug concentration monitoring. Quantitative determination of isavuconazole concentrations in plasma was performed using liquid chromatography-tandem mass spectrometry (LC-MS/MS).

Первичные конечные точки

• Isavuconazole plasma concentration [Срок оценки: after 3 days of antibiotic therapy]

Критерии участия

Критерии включения

• 1.Aged over 60 years, with no restriction on gender; 2.Diagnosed with invasive aspergillosis and mucormycosis; 3.Receiving isavuconazole treatment (including loading dose and maintenance dose), with an anticipated treatment duration of ≥ 48 hours; 4.Clinically stable and able to undergo blood sample collection; 5.Having consented to participate in the study and voluntarily signed the informed consent form.

Критерии исключения

• 1.Allergy to any component of isavuconazole; 2.Pregnant women, breastfeeding women, or patients planning to become pregnant in the near future; 3.Inability to collect an adequate blood sample due to the patient's condition or technical reasons; 4.Patients deemed unsuitable for participation in the study by the investigator.

Критерии приведены из реестра в оригинале (на английском). Окончательную оценку соответствия проводит исследовательский центр.

Дизайн исследования

Модель наблюдения

Когортное

Центры проведения

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Идентификаторы

NCT: NCT07496008 · S2025-448-03

Первоисточники (государственные реестры)

• ClinicalTrials.gov (NIH, США)

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