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[Example of active therapeutic follow-up: itraconazole]
J C Levron1, L Moing, E Chwetzoff
1Janssen Research Foundation, Centre de Recherche Janssen-Cilag, France.
Abstract:
The systematic fungal infections are very serious diseases, the crude mortality in invasive aspergillosis reaches 75 to 100 per cent. Systemic mycosis tends to develop in immunocompromised patients with subsequent physiopathological state, causing a risk of impairment in their digestive absorption potential; in addition these patients are polymedicated and the emergence of multiple drug interactions is frequent. Itraconazole is a very potent antifungal drug with large safety margin and the drug monitoring to maintain a satisfactory plasma level. Immunocompromised patients with suspected malabsorption and treated with oral capsule itraconazole were monitored during two years. In such difficult patients (approximately equal to 500 cases), the result has shown good trough steady-state plasma levels in 72 per cent and insufficient in 28 per cent of the observed patients. However concomitant treatments with antacids produce, in a lot of cases (approximately equal to 48 per cent), a noticeable decrease of the itraconazole availability for these patients. A training program was established to perform the analytical determination of itraconazole and hydroxyitraconazole in biological samples by HPLC method. Analytical validation procedures were associated to this training program which included 115 scientific, technical staff (pharmacists, biochemists ...) from 56 hospitals and institutes.
Insights
Systemic fungal infections are serious, with invasive aspergillosis mortality up to 100%. Monitoring itraconazole (ITR) levels in immunocompromised patients is crucial, as antacids significantly reduce ITR absorption.
Area of Science:
- Mycology
- Pharmacology
- Clinical Medicine
Context:
- Systemic fungal infections, like invasive aspergillosis, present high mortality rates (75-100%).
- Immunocompromised patients are susceptible to mycosis and often experience impaired digestion and drug interactions due to polymedication.
- Itraconazole is a potent antifungal agent requiring therapeutic drug monitoring for optimal plasma levels.
Purpose:
- To monitor itraconazole plasma levels in immunocompromised patients with suspected malabsorption.
- To assess the impact of concomitant antacid use on itraconazole bioavailability.
- To establish a training program for analytical determination of itraconazole and hydroxyitraconazole using HPLC.
Summary:
- Two-year monitoring of 500 immunocompromised patients showed 72% achieved adequate itraconazole trough steady-state plasma levels.
- A significant decrease in itraconazole availability (48%) was observed when co-administered with antacids.
- A training program using HPLC for biological sample analysis was developed and implemented across 56 institutions.
Impact:
- Highlights the critical need for therapeutic drug monitoring of itraconazole in vulnerable patient populations.
- Identifies antacid use as a significant factor reducing itraconazole efficacy, necessitating careful co-prescription.
- Facilitates standardized and accurate analytical methods for itraconazole quantification in clinical settings.