Pharmacokinetic profile of cyclosporine A and G and their effects on cellular immunity and glucose tolerance in male and female Wistar rats.
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| Abstract |
This study examined the effects of the widely used immunosuppressor cyclosporine A and of one of its derivatives, cyclosporine G, on glucose tolerance, cellular immunity, and renal and hepatic function, in relation to their pharmacokinetic profile in Wistar rats. After 3 weeks of daily cyclosporine A doses of 10 mg/kg body weight plasma cyclosporine levels were higher in male than in female rats. This was associated in male rats with marked decrease in lymphocyte subsets, affecting particularly the OX19+ T cells, with glucose intolerance, and an increase in plasma creatinine. The female rats had none of these effects. After 3 weeks of daily cyclosporine G doses of 10 mg/kg body weight, plasma cyclosporine levels were higher in male than female animals, and higher than with cyclosporine A in both sexes. Similar cellular immune effects and glucose intolerance were seen in male rats, but of a lesser magnitude than with cyclosporine A. No increase in creatinine was seen, but rats of both sexes treated with cyclosporine G had elevated plasma bilirubin. We conclude that (1) both cyclosporine A and G can cause glucose intolerance, (2) the cyclosporine plasma levels are higher in male than in female rats and with cyclosporine G than with cyclosporine A, for the same oral dose, (3) the absence of glucose intolerance, nephrotoxicity, and cellular immune changes in female rats treated with cyclosporine A is related to their lower cyclosporine levels, and (4) cyclosporine G is less nephrotoxic than cyclosporine A, but more hepatotoxic.
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| Authors | M Faraci, C Vigeant, J F Yale |
| Journal | Transplantation (Transplantation) Vol. 45 Issue 3 Pg. 617-21 (Mar 1988) ISSN: 0041-1337 [Print] United States |
| PMID | 3347939 (Publication Type: Comparative Study, Journal Article, Research Support, Non-U.S. Gov't) |
| Chemical References |
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