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Cyclosporine A disposition, hepatic and renal tolerance in Wistar rat

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Maerckx, Cédric [UCL] Lombard, Catherine [UCL] Tondreau, Tatiana [UCL] Najimi, Mustapha [UCL] Wallemacq, Pierre [UCL] Sokal, Etienne [UCL]

Cyclosporine A, a potent calcineurin inhibitor, has been widely used in organ transplantation and in the treatment of autoimmune diseases. It has however been shown to induce serious renal and hepatic side effects. The drug is also used in preclinical studies, but with little published information on the optimal dose and route of administration in rodents. Objectives of this study were to identify efficient and safe doses of cyclosporine A in rodent and to assess its effects on hepatic and renal functions. For this purpose, we tested the effects of different doses and administration routes of cyclosporine A (5, 2.5 and 1 mg/kg) administered during 28 days intraperitoneally, or by gastric feeding on Wistar rats. Our data indicate that rats injected intraperitoneally with 5 mg/kg/2d (every two days) exhibited trough cyclosporine A levels within known therapeutic range in human, but were subject to blood cyclosporine A accumulation, whereas the 5 mg/kg/d gavage resulted in only a small cyclosporine A accumulation over time. In both cases this accumulation was not deleterious to renal and hepatic functions, as shown by transaminase, urea, creatinine and bilirubin measurements.

Document type Article de périodique (Journal article) – Article de recherche
Publication date 2016
Language Anglais
Journal information "Immunopharmacology and Immunotoxicology" - Vol. 38, no. 6, p. 390-394 (2016)
Peer reviewed yes
Publisher Informa Healthcare ((United Kingdom) London)
issn 0892-3973
e-issn 1532-2513
Publication status Publié
Affiliations UCL - SSS/IREC/PEDI - Pôle de Pédiatrie
UCL - (SLuc) Service de gastro-entérologie et hépatologie pédiatrique
UCL - SSS/IREC/LTAP - Louvain Centre for Toxicology and Applied Pharmacology
UCL - (SLuc) Service de biochimie médicale
Keywords Hepatic and renal enzymes ; Intraperitoneal administration ; Kinetics ; Organ toxicity ; Per os administration
Links
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Bibliographic reference Maerckx, Cédric ; Lombard, Catherine ; Tondreau, Tatiana ; Najimi, Mustapha ; Wallemacq, Pierre ; et. al. Cyclosporine A disposition, hepatic and renal tolerance in Wistar rat. In: Immunopharmacology and Immunotoxicology, Vol. 38, no. 6, p. 390-394 (2016)
Permanent URL http://hdl.handle.net/2078.1/176644