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Human autopsy tissue concentrations of mitoxantrone
Cancer Treatment Reports
|November 1, 1986
Summary
Mitoxantrone drug levels remain detectable in human tissues long after administration, with highest concentrations in the thyroid, liver, and heart. These findings suggest a link between cardiac mitoxantrone levels and cardiotoxicity.
Area of Science:
- Pharmacology
- Toxicology
- Oncology
Background:
- Mitoxantrone is an anthracenedione chemotherapy agent used in treating various cancers and multiple sclerosis.
- Understanding mitoxantrone's tissue distribution and persistence is crucial for evaluating its efficacy and toxicity profile.
Purpose of the Study:
- To quantify mitoxantrone concentrations in autopsy human tissues.
- To investigate the relationship between mitoxantrone dosage, time post-administration, and tissue levels.
- To explore potential correlations between tissue mitoxantrone levels and observed cardiotoxicity.
Main Methods:
- A sensitive high-performance liquid chromatography (HPLC) method was employed.
- Analysis of autopsy tissue samples from 11 patients who received intravenous mitoxantrone.
- Measurement of mitoxantrone levels at intervals of 10-272 days antemortem.
Main Results:
- Mitoxantrone was detectable in all patient tissues, with concentrations correlating to cumulative dose and decreasing slowly over time.
- Highest mitoxantrone concentrations were found in the thyroid, liver, and heart; lowest in the brain.
- Tumor mitoxantrone levels varied significantly, generally lower than surrounding normal tissues, with highest levels in intrahepatic and lowest in intracerebral tumors.
Conclusions:
- Mitoxantrone exhibits prolonged retention in human tissues, particularly the thyroid, liver, and heart.
- Elevated cardiac mitoxantrone concentrations may contribute to drug-induced cardiotoxicity.
- Further research is needed to elucidate the full impact of tissue mitoxantrone levels on treatment outcomes and adverse effects.