Serum level directed itraconazole therapy in allergic bronchopulmonary aspergillosis

Kshitij Agarwal, Roger Bruggemann, Anuradha Chowdhary, J.F. Meis, S.N. Gaur


Background Itraconazole (ITZ) is an alternative to steroids in the treatment of allergic bronchopulmonary aspergillosis (ABPA) but therapeutic drug monitoring (TDM) is warranted due to erratic absorption and early relapse.

Aim To correlate serum ITZ levels with clinical outcomes in ABPA.

Methods ITZ capsules 400mg/day for 6 months were administered as monotherapy to 30 consecutive patients in stage 4/5 of ABPA between Jan'13 to Jun'13. High-performance liquid chromatography was done on serum samples collected after 2-4 weeks to measure concentrations of ITZ and its active metabolite hydroxy-ITZ (OHITZ); ITZ levels of >2mg/L were considered adequate. Total and Aspergillus species specific IgE, leucocyte count (TLC), eosinophil count (AEC) and precipitins were recorded before and thereafter. Any relapse was noted till 2 years.

Results Mean serum concentration of ITZ and OHITZ was 0.79±0.2 and 1.2±0.3mg/L respectively. Total IgE (9.9±1.4 vs 6.5±1.2×103IU/mL), specific IgE (42.98±3.9 vs 34.1±4.8KUA/L), TLC (10.6±0.6 vs 9.7±0.7×103cells/µL) and AEC (1.0±0.1 vs 0.6±0.09×103cells/µL) reduced significantly. Remission was achieved in 64% but 52% relapsed after 3months. Serum ITZ and OHITZ levels correlated negatively with total IgE, specific IgE, TLC, AEC, relapse and time to relapse but only those between ITZ (r=0.049) and OHITZ (r=0.039) with duration to relapse were significant. Adequacy of ITZ and OHITZ significantly related with remissions(P=0.039).

Conclusion ITZ monotherapy is effective in treating ABPA therefore TDM should be routinely undertaken. Adequate serum drug levels imply remissions but do not correlate well with markers of disease severity. Relapse may be prevented by prolonged drug use.


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European Respiratory Society 2016
    • ERS 26th (2016)