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Cyclosporine pharmacokinetics and effect in the Type I diabetic rat model

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Summary

Recent clinical studies have demonstrated the potential benefit of the T-cell-specific immunosuppressant, cyclosporine, in the treatment of Type I insulin-dependent diabetes. In the present study, steady-state cyclosporine pharmacokinetics, fasting glucose and insulin levels and renal function were examined in stable insulin-dependent diabetic rats and compared to non-diabetic rats. Mean creatinine clearance 30 days following diabetes induction was not significantly different from saline controls. Cyclosporine treatment (5 mg/kg/day i.v. for 13 days) did not significantly alter creatinine clearance in either group; however, renal function of vehicle-treated diabetic rats was markedly reduced compared to other groups. Serum insulin concentrations were significantly greater in diabetic rats treated with cyclosporine compared to the control group (35.1±22.7 vs. 16.0±8.1 μU/ml;P<0.05). Glucose levels were proportionately reduced in diabetic rats treated with cyclosporine. Area under the concentration-time curve, half-life and volume of distribution of cyclosporine were significantly reduced in diabetic rats compared to non-diabetic controls. In summary, the pharmacokinetics and pharmacodynamics of cyclosporine were significantly different in the insulin-dependent diabetic rat model compared to normal controls. Furthermore, short-term cyclosporine therapy reduced the extent of experimental diabetic nephropathy observed in this model.

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Authors and Affiliations

  1. Department of Pharmaceutics, Texas Medical Center, University of Houston, Houston, Texas, USA

    L. J. Brunner, L. V. Iyer, K. Vadiei, W. V. Weaver & D. R. Luke

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  1. L. J. Brunner
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  2. L. V. Iyer
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  3. K. Vadiei
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  4. W. V. Weaver
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  5. D. R. Luke
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Brunner, L.J., Iyer, L.V., Vadiei, K. et al. Cyclosporine pharmacokinetics and effect in the Type I diabetic rat model. Eur. J. Drug Metab. Pharmacokinet. 14, 287–292 (1989). https://doi.org/10.1007/BF03190113

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  • DOI: https://doi.org/10.1007/BF03190113

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