Toxicity of a particulate formulation for the intraperitoneal application of mitoxantrone.
Mitoxantrone (MXN) has demonstrated therapeutic efficacy in the intraperitoneal treatment of malignancies. However, severe local toxicity is dose limiting. Therefore, a particulate formulation of MXN, the drug incorporated in albumin microspheres, was evaluated concerning tolerability. Survival rates as well as alterations in body weight, food intake, water intake, urine volume, urine specific gravity, urine protein content, and complete blood count were observed following single or multiple intraperitoneal injections of MXN solution, dispersions containing MXN-loaded microspheres or unloaded microspheres, and the injection vehicle to female and male Sprague-Dawley rats. Applied MXN dosage was equivalent to 30 mg/m2 body surface area. Unloaded microspheres were well tolerated without signs of toxicity. Application of MXN solution or MXN-loaded microspheres resulted in similar survival rates (56% 9 weeks after single injection) and in a comparable bone marrow toxicity (mainly leucopenia). Body weight, food and water intake as well as urine volume were decreased following application of MXN solution, whereas a progressive gain in weight and no remarkable alterations in nutrition and urine excretion were noted after administration of MXN-loaded and unloaded microspheres, or of the injection vehicle. In conclusion, intraperitoneal injection of MXN incorporated in albumin microspheres exhibits in part less toxicity than conventional treatment.
Luftensteiner
C P
CP
Institute of Pharmaceutical Technology, University of Vienna, Althanstrasse 14, A-1090, Vienna, Austria.
Schwendenwein
I
I
Eichler
H G
HG
Paul
B
B
Wölfl
G
G
Viernstein
H
H
D000818:Animals; D000970:Antineoplastic Agents / Q000008:administration & dosage / Q000633:toxicity; D001772:Blood Cell Count; D001835:Body Weight / Q000187:drug effects; D004435:Eating / Q000187:drug effects; D005260:Female; D006801:Humans; D007274:Injections, Intraperitoneal; D008297:Male; D008863:Microspheres; D008942:Mitoxantrone / Q000008:administration & dosage* / Q000633:toxicity*; D010316:Particle Size; D010538:Peritonitis / Q000139:chemically induced / Q000473:pathology; D051381:Rats; D017207:Rats, Sprague-Dawley; D012737:Sex Factors; D016019:Survival Analysis; D014554:Urination / Q000187:drug effects
D000970:Antineoplastic Agents; D008942:Mitoxantrone