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Titolo:
Preclinical profile of the monodisperse iodinated macromolecular blood pool agent P743
Autore:
Idee, JM; Port, M; Robert, P; Raynal, I; Prigent, P; Dencausse, A; Le Greneur, S; Tichkowsky, I; Le Lem, G; Bourrinet, P; Mugel, T; Benderbous, S; Devoldere, L; Bourbouze, R; Meyer, D; Bonnemain, B; Corot, C;
Indirizzi:
Guerbet, Div Res, Aulnay Sous Bois, France Guerbet Aulnay Sous Bois France rbet, Div Res, Aulnay Sous Bois, France Hotel Dieu, Dept Radiol, Paris, France Hotel Dieu Paris FranceHotel Dieu, Dept Radiol, Paris, France Fac Pharm, Biochem Lab, Paris, France Fac Pharm Paris FranceFac Pharm, Biochem Lab, Paris, France
Titolo Testata:
INVESTIGATIVE RADIOLOGY
fascicolo: 1, volume: 36, anno: 2001,
pagine: 41 - 49
SICI:
0020-9996(200101)36:1<41:PPOTMI>2.0.ZU;2-W
Fonte:
ISI
Lingua:
ENG
Soggetto:
ACUTE-RENAL-FAILURE; CONTRAST AGENTS; PATHOPHYSIOLOGY; POLYMER; MODEL; RAT; CT;
Tipo documento:
Article
Natura:
Periodico
Settore Disciplinare:
Clinical Medicine
Life Sciences
Citazioni:
32
Recensione:
Indirizzi per estratti:
Indirizzo: Idee, JM Guerbet, Div Biol, BP 50400, F-95943 Roissy Charles De Gaulle, France Guerbet BP 50400 Roissy Charles De Gaulle France F-95943 France
Citazione:
J.M. Idee et al., "Preclinical profile of the monodisperse iodinated macromolecular blood pool agent P743", INV RADIOL, 36(1), 2001, pp. 41-49

Abstract

RATIONALE AND OBJECTIVES. TO summarize the chemical synthesis, physicochemical characterization, pharmacokinetic behavior, and biological evaluation of P743, a new macromolecular iodinated contrast medium. METHODS. The synthesis and molecular modeling of the iodinated macromolecule P743 are described. The pharmacokinetic profile was established in rabbits and rats. Acute toxicity in mice, renal tolerance in normal rabbits, andrenal tolerance in uninephrectomized, dehydrated rats undergoing selectiveintrarenal injection was evaluated. In vitro permeability effects on isolated mastocytes and on the coagulation pathways were carried out. Computed tomography vascular imaging was performed after intravenous injection of P743 (300 mg I/kg) in rabbits and compared with the nonspecific nonionic agentiobitridol,RESULTS. P743 is a monodisperse, macromolecular iodinated contrast medium. In both rabbits and rats, P743 showed a pharmacokinetic profile consistentwith that of a rapid-clearance blood-pool agent. Its diffusion through theendothelium was found to be low in vitro, thus confirming early confinement of this macromolecule, unlike nonspecific contrast media. In both species, P743 was excreted by glomerular filtration. Acute toxicity disclosed no mortality at the highest volume that could be injected into mice, leading toa median lethal dose greater than 8.9 g I/kg, Renal tolerance was found tobe good in both euvolemic rabbits and uninephrectomized, dehydrated rats. No histamine or leukotriene B-4 release was found on RBL-2H3 isolated mastocytes. P743 did not interfere with the coagulation pathways. Imaging experiments confirmed that P743 remains in the vascular compartment for a longer time than does iobitridol, thus allowing vascular enhancement that is twiceas high as that of iobitridol in the recirculation phase. CONCLUSIONS. The pharmacokinetic and imaging profiles of P743, a new, monodisperse, macromolecular blood-pool iodinated contrast medium, were consistent with those of a rapid-clearance blood-pool agent. Its initial safety profile is satisfactory. Further experimental imaging studies are required todefine the clinical interest in such molecules.

ASDD Area Sistemi Dipartimentali e Documentali, Università di Bologna, Catalogo delle riviste ed altri periodici
Documento generato il 16/07/20 alle ore 16:39:06