title: Tolerability and toxicological profile of pixantrone (Pixuvri®) in juvenile mice. Comparative study with doxorubicin.
abstract: The tolerability of pixantrone dimaleate (Pixuvri(®)), an aza-anthracenedione for non-Hodgkin lymphoma, was assessed in juvenile mice after intraperitoneal injection. Twenty animals/sex/dose received pixantrone 15 or 27 mg/kg/day on Post-Natal-Days (PND) 10, 13, 17, 20, 35, 39 and 42 in comparison with doxorubicin, 3 mg/kg/day. Animals were sacrificed on PND 42, 73 and 96. All pixantrone animals survived, while doxorubicin induced 52.5% mortality and the surviving animals were sacrificed early due to severe toxicity. Recoverable bone marrow toxicity (pixantrone), and toxicity to thymus and reproductive organs (pixantrone, doxorubicin) were observed without nephro- or hepatotoxicity. Pixantrone was measurable in plasma up to 2h (occasionally 6h) post-dose. At PND 42, mean Cmax and AUC values increased proportionally with dose, without gender difference or accumulation. Pixantrone showed minimal cardiotoxicity in males and negligible in females at PND 96. Doxorubicin induced significant heart weight reduction at PND 42, however early sacrifice impeded further cardiac assessments.
authors.affiliation: Accelera S.r.l., Viale Pasteur 10, 20014 Nerviano, Milan, Italy. Electronic address: monica.longo@accelera.org.
authors.forename: Monica
authors.initials: M
authors.lastname: Longo
authors.affiliation: Accelera S.r.l., Viale Pasteur 10, 20014 Nerviano, Milan, Italy.
authors.forename: Paola
authors.initials: P
authors.lastname: Della Torre
authors.affiliation: CTI Expert Consultant, Italy.
authors.forename: Cecilia
authors.initials: C
authors.lastname: Allievi
authors.affiliation: CTI Expert Consultant, Italy.
authors.forename: Alberto
authors.initials: A
authors.lastname: Morisetti
authors.affiliation: Cell Therapeutics, Inc, United States.
authors.forename: Suliman
authors.initials: S
authors.lastname: Al-Fayoumi
authors.affiliation: Cell Therapeutics, Inc, United States.
authors.forename: Jack W
authors.initials: JW
authors.lastname: Singer
mesh_terms: D000818:Animals; D000903:Antibiotics, Antineoplastic / Q000633:toxicity*; D001835:Body Weight / Q000187:drug effects; D001853:Bone Marrow / Q000473:pathology; D004317:Doxorubicin / Q000633:toxicity*; D005260:Female; D006331:Heart Diseases / Q000139:chemically induced / Q000473:pathology; D007546:Isoquinolines / Q000633:toxicity*; D007674:Kidney Diseases / Q000139:chemically induced / Q000473:pathology; D008297:Male; D051379:Mice; D008813:Mice, Inbred ICR; D009929:Organ Size / Q000187:drug effects; D059005:Topoisomerase II Inhibitors / Q000633:toxicity*
chemical_list: D000903:Antibiotics, Antineoplastic; D007546:Isoquinolines; D059005:Topoisomerase II Inhibitors; D004317:Doxorubicin; C086548:pixantrone
keywords: Anticancer; Doxorubicin; Juvenile; Pixantrone; Pixuvri; Preclinical