Coupling of mitoxantrone to poly(I).poly(C) reduces absorption after intraperitoneal administration

Area of Science:

• Oncology
• Pharmacology
• Biochemistry

Background:

• Direct intraperitoneal chemotherapy is used for peritoneal carcinosis.
• Systemic absorption of chemotherapeutic agents can lead to side effects.
• Mitoxantrone (M) is an intercalating cytostatic agent used in chemotherapy.

Purpose of the Study:

• To investigate if coupling mitoxantrone (M) to macromolecular polynucleotides reduces systemic absorption.
• To evaluate the impact of poly(I).poly(C) on mitoxantrone pharmacokinetics after intraperitoneal administration.

Main Methods:

• A cross-over study involving 5 patients with peritoneal carcinosis.
• Administration of free mitoxantrone (30 mg/m2) or mitoxantrone mixed with poly(I).poly(C) (90 mg/m2) intraperitoneally.
• Plasma levels of mitoxantrone were measured using HPLC assay.

Main Results:

• Peak plasma levels of mitoxantrone were significantly lower when coupled with poly(I).poly(C) (28 +/- 4 ng/ml) compared to free mitoxantrone (62 +/- 12 ng/ml) (p < 0.0025).
• Area under the curve (AUC0-24h) for mitoxantrone was also reduced when coupled with poly(I).poly(C) (481 +/- 57 ng X h/ml) versus free mitoxantrone (583 +/- 126 ng X h/ml) (p < 0.025).

Conclusions:

• Coupling mitoxantrone to poly(I).poly(C) effectively reduces its systemic absorption following intraperitoneal administration.
• This approach may be a strategy to mitigate side effects associated with mitoxantrone chemotherapy.