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Bioassay for serum itraconazole concentrations using hydroxyitraconazole standards
D Law1, C B Moore, D W Denning
1Department of Microbiology, Hope Hospital, Salford, United Kingdom.
Antimicrobial Agents and Chemotherapy
|July 1, 1994
Summary
Monitoring itraconazole levels is crucial for effective treatment. A new bioassay using hydroxyitraconazole standards accurately measures both itraconazole and its active metabolite in patient serum.
Area of Science:
- Pharmacology
- Clinical Chemistry
- Mycology
Background:
- Low itraconazole serum concentrations are linked to treatment failure.
- Interpatient variability and drug interactions affect itraconazole efficacy.
- Current HPLC methods do not measure the active hydroxyitraconazole metabolite.
Purpose of the Study:
- To develop and validate a bioassay for total serum itraconazole and hydroxyitraconazole.
- To compare the new bioassay with existing HPLC methods.
- To assess the accuracy and reproducibility of the hydroxyitraconazole-standardized bioassay.
Main Methods:
- Developed a bioassay using hydroxyitraconazole standards for total drug measurement.
- Assayed 40 clinical samples using both HPLC and the new bioassay.
- Compared results from bioassay (with itraconazole and hydroxyitraconazole standards) and HPLC.
Main Results:
- The bioassay with hydroxyitraconazole standards showed excellent correlation with HPLC (r=0.98).
- Reproducibility was acceptable, with minor errors at concentration extremes.
- The ratio of hydroxyitraconazole to itraconazole varied significantly (0.76–3.2) in patient samples.
Conclusions:
- A bioassay using hydroxyitraconazole standards provides accurate and reproducible total itraconazole and hydroxyitraconazole measurements.
- This method correlates well with HPLC, improving therapeutic drug monitoring.
- Both itraconazole and hydroxyitraconazole contribute equivalently in patient samples, despite differences in bioassay inhibition zones.