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

Chinese PLA General Hospital (301 Hospital)

Status: Not yet enrolling

Conditions: Invasion Pulmonary Mycosis; Isavuconazole

Treatments: Diagnostic Test: Liquid chromatography-tandem mass spectrometry

Study type: Observational

Funder types: Other

Identifiers

NCT07496008

S2025-448-03

Details and patient eligibility

About

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.

Enrollment: 150 estimated patients

Sex: All

Ages: 60+ years old

Volunteers: No Healthy Volunteers

Inclusion criteria

• 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.

Exclusion criteria

• 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.

Trial design

150 participants in 1 patient group

isavuconazole

Description:

Clinical Blood Sampling Protocol for isavuconazole in Geriatric Patients: Elderly patients received isavuconazole. After 5-7 days of antibiotic therapy (steady-state achievement), blood sampling was performed as follows: Trough Concentration: A 3-mL peripheral blood sample was collected from the antecubital vein pre-dose (before the next scheduled administration) using EDTA-containing Vacutainers®. Peak Concentration: A blood sample was drawn immediately after completion of the intravenous infusion. All blood specimens were centrifuged at 2500 × g for 10 minutes. Plasma samples were stored at -20°C and analyzed within 1 week of collection via liquid chromatography-tandem mass spectrometry (LC-MS/MS).

Treatment:

Diagnostic Test: Liquid chromatography-tandem mass spectrometry