Tolerability and toxicological profile of pixantrone (Pixuvri®) in juvenile mice. Comparative study with doxorubicin.

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.

Potent trophic activity of spermidine supramolecular complexes in in vitro models.

Aim: To test the growth-promoting activity of the polyamine spermidine bound to various polymeric compounds in supramolecular complexes.

Methods: A thiazolyl blue cell viability assay was used to determine the growth-promoting potency of spermidine-supramolecular complexes in a human skin fibroblast cell line exposed to spermidine and different spermidine-supramolecular complexes that were obtained by combining spermidine and polyanionic polymers or cyclodextrin. Reconstituted human vaginal epithelium was exposed to a specific spermidine-supramolecular complex, i.

Contrast-enhanced MRI of murine sponge model for progressive angiogenesis assessed with gadoteridol (ProHance) and gadocoletic acid trisodium salt (B22956/1).

Purpose: To investigate the potential value of MRI for noninvasive assessment of angiogenesis in a murine model exploiting the properties of two contrast agents, gadoteridol (ProHance) and gadocoletic acid trisodium salt (B22956/1).

Materials And Methods: Biocompatible sponges were implanted in both mice flanks. Stimulated sponges contained human recombinant basic fibroblast growth factor (bFGF) as the angiogenic agent; control sponges contained vehicle.

Dose-related effects of repeated ETC-216 (recombinant apolipoprotein A-I Milano/1-palmitoyl-2-oleoyl phosphatidylcholine complexes) administrations on rabbit lipid-rich soft plaques: in vivo assessment by intravascular ultrasound and magnetic resonance imaging.

Objectives: This study sought to evaluate in vivo the minimal dose of apolipoprotein (apo) A-I(Milano) phospholipid complex (recombinant apoA-I(Milano) and 1-palmitoyl-2-oleoyl phosphatidylcholine complexes [ETC-216]) able to induce atherosclerosis regression in a rabbit model of lipid-rich plaques.

Background: A single high dose of recombinant apoA-I(Milano) has promoted atherosclerosis regression in animal models. More recently, regression of atherosclerosis was achieved in coronary patients by repeated infusions of ETC-216.

Toxicological assessment of gadolinium release from contrast media.

In vivo gadolinium release was evaluated for MultiHance, Omniscan and Gadovist estimating gadolinium content in liver, kidneys, spleen, femur and brain after single or repeated intravenous administrations to rats at 1 mmol/kg. Gadolinium acetate (GdAc) at a daily dose of 0.03 mmol/kg and physiological saline were used as positive and negative controls, respectively.

High-performance liquid chromatographic determination of the magnetic resonance imaging contrast agent Gadocoletate ion in human plasma, urine and faeces.

Gadocoletate ion is a new paramagnetic intravascular contrast agent for magnetic resonance imaging (MRI). An high-performance liquid chromatographic method for assaying Gadocoletate ion in human plasma, urine and faecal samples is described. The analysis is based on the reversed-phase chromatographic separation of Gadocoletate ion from the endogenous components of the biological matrices and its detection during elution by ultraviolet light absorption at 200 nm.

Gadocoletic acid trisodium salt (b22956/1): a new blood pool magnetic resonance contrast agent with application in coronary angiography.

Rationale And Objectives: Inversion recovery, three-dimensional, gradient-recalled echo magnetic resonance coronary angiography (IR-3D-GRE-MRCA), performed after administration of an intravascular T1-relaxing agent with prolonged permanence in the blood, is one of the most promising approaches to noninvasive magnetic resonance imaging (MRI) of the coronaries. The aim of the present study was the evaluation of the physicochemical properties in solution, pharmacokinetics, elimination from the body, protein binding, and signal enhancement characteristics of gadocoletic acid trisodium salt (B22956/1), a candidate gadolinium-based MRI contrast agent for coronary angiography.

Methods: The pharmacokinetics and elimination from the body of gadocoletate ion, the contrastographically active component of gadocoletic acid trisodium salt, was evaluated after intravenous administration in rats and monkeys, using for assays high-performance liquid chromatography, x-ray fluorescence, and inductively coupled plasma atomic emission spectrometry.

Margins of safety of intravascular contrast media: body weight, surface area or toxicokinetic approach?

The margin of safety of a drug is defined as the ratio between toxicity in animals and safety in humans. For intravascular contrast media, the margin of safety is traditionally the ratio between LD50 and diagnostic dose, both doses being based on bodyweight. The shift to surface area dramatically reduces this margin to unacceptable values.

Conjugates of gadolinium complexes to bile acids as hepatocyte-directed contrast agents for magnetic resonance imaging.

A series of structurally different Gd(III) conjugates incorporating a bile acid moiety have been prepared. Polyaminopolycarboxylic ligands such as diethylenetriaminepentaacetic acid (DTPA) and 1,4,7,10-tetraazacyclododecane-1,4,7,10-tetracetic acid (DOTA) have been selected as chelating subunit for the Gd(III) ion. Cholic acid, cholylglycine, and cholyltaurine have been incorporated as the bile acid moieties.