Bioavailability of orally administered mesna.

Area of Science:

• Pharmacokinetics
• Drug Metabolism
• Urology

Background:

• Sodium 2-mercaptoethane sulfonate (mesna) is used to prevent hemorrhagic cystitis.
• Understanding mesna's oral bioavailability is crucial for optimizing its therapeutic efficacy.

Purpose of the Study:

• To evaluate the bioavailability and pharmacokinetic profile of orally administered mesna.
• To determine the urinary excretion of mesna and its metabolite, dimesna.
• To assess the duration of protective mesna concentrations in urine.

Main Methods:

• Single and multiple oral and intravenous administrations of mesna in healthy probands and tumor patients.
• Measurement of urinary excretion of reactive thiol groups and mesna disulfide (dimesna).
• Analysis of mesna concentration-time profiles in urine.

Main Results:

• Oral mesna demonstrated significant bioavailability, with approximately 52.5% of the dose excreted as reactive thiol groups.
• Urinary excretion of thiol groups after i.v. administration was around 48.7%.
• Individual variability in elimination patterns and time to reach protective urinary concentrations (100 µg/ml) was noted, with thresholds reached after 13.1-18.5 hours post-dose.

Conclusions:

• Oral mesna is well-absorbed and excreted as active thiol groups.
• Significant inter-individual differences in mesna pharmacokinetics necessitate careful dosing and monitoring.
• Further investigation into factors influencing mesna elimination is warranted.