Formulation and evaluation of irinotecan suppository for rectal administration

Area of Science:

• Pharmacology
• Pharmaceutical Sciences
• Analytical Chemistry

Background:

• Irinotecan is a vital chemotherapy drug, but its administration routes and bioavailability require further investigation.
• Developing efficient drug delivery systems is crucial for optimizing cancer treatment outcomes.

Purpose of the Study:

• To prepare and characterize an irinotecan suppository using the moulding method.
• To develop and validate a sensitive fluorescence-based High-Performance Liquid Chromatography (HPLC) method for quantifying irinotecan in plasma.
• To investigate and compare the pharmacokinetics of irinotecan following intravenous and rectal administration in rabbits.

Main Methods:

• Irinotecan suppositories were prepared using a homogeneous blend and the moulding technique.
• A sensitive and specific fluorescence detection method coupled with HPLC was established and validated for plasma irinotecan analysis.
• Pharmacokinetic parameters were determined in rabbits after single intravenous (50 mg/kg) and rectal (100 mg/kg) doses of irinotecan.

Main Results:

• The HPLC-fluorescence method demonstrated sensitivity and specificity for irinotecan determination.
• Intravenous irinotecan exhibited rapid plasma concentration decline (t1/2 ≈ 7.6 h).
• Rectal administration resulted in a peak plasma concentration of 5.3 μg/ml at 4 hours, achieving approximately 50.6% absolute bioavailability.

Conclusions:

• The developed moulding method is suitable for preparing irinotecan suppositories.
• The validated HPLC-fluorescence assay provides a reliable tool for pharmacokinetic studies of irinotecan.
• Rectal administration of irinotecan offers a potential alternative route with significant bioavailability, warranting further clinical investigation.