Variable bioavailability following repeated oral doses of etoposide

Area of Science:

• Pharmacology
• Oncology
• Clinical Pharmacy

Background:

• Etoposide oral bioavailability exhibits significant inter-patient variability.
• Intra-patient variability in etoposide bioavailability with repeated dosing is not well-characterized.

Purpose of the Study:

• To assess the within-patient variability of oral etoposide bioavailability over three successive days.
• To determine if etoposide accumulates or if absorption changes during short-term oral therapy.

Main Methods:

• Seven patients with relapsed small cell lung carcinoma received oral etoposide (400 mg) daily for three days.
• Plasma etoposide concentrations were quantified using high-performance liquid chromatography.
• Urinary excretion of etoposide was also measured.

Main Results:

• Within-patient coefficients of variation for peak plasma concentrations ranged from 19-45%.
• Within-patient coefficients of variation for area under the plasma concentration-time curve ranged from 16-53%.
• No evidence of absorption improvement/worsening or drug accumulation was observed; urinary excretion remained below 25%.

Conclusions:

• Oral etoposide bioavailability is inconsistent during multi-day therapy, posing risks of underdosing or toxicity.
• Single-day pharmacokinetic monitoring may not accurately reflect total bioavailability over a treatment course.
• Reliable assessment of prolonged oral etoposide therapy outcomes may require using intravenous administration.