Cyclosporine A disposition, hepatic and renal tolerance in Wistar rat.

Immunopharmacol Immunotoxicol

a Laboratory of Pediatric Hepatology and Cell Therapy, Institut de Recherche Clinique et Expérimentale (IREC) , Université Catholique de Louvain, Brussels , Belgium.

Published: December 2016

AI Article Synopsis

  • Cyclosporine A is a potent drug used in organ transplantation and autoimmune diseases but can cause serious kidney and liver side effects.
  • Different dosing and administration methods were tested in Wistar rats to find safe and effective levels of cyclosporine A.
  • Results showed that intraperitoneal injection caused drug accumulation but did not harm organ functions, while gastric feeding led to minimal accumulation without adverse effects.

Article Abstract

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.

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Source
http://dx.doi.org/10.1080/08923973.2016.1233979DOI Listing

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