Pharmacokinetic characteristics and clinical efficacy of generic cyclosporine formulations compared to Sandimmune Neoral
Abstract
The current study was aimed at investigation of pharmacokinetic parameters and of clinical efficacy of generic cyclosporine in comparison with Sandimmune Neoral. To evaluate the pharmacokinetic parameters of different cyclosporine formulations, 159 comprehensive pharmacokinetic investigations were accomplished in 115 kidney transplant patients. 71 (45%) out of 159 pharmacokinetic studies were performed in patients treated with Neoral, whereas in 88/159 (55%) cases participants received generic cyclosporine. AUC calculations based on dosing interval concentration values were fulfilled using linear trapezoidal rule. Clinical efficacy of generic cyclosporine was evaluated in a retrospective study of 500 recipients that had undertaken cadaver kidney grafting since 2002 year. 304 participants were treated with Neoral and the other 196 - with generics (mainly Consupren) at least for 3 months. The prevalence of late acute rejection and of chronic allograft dysfunction was analyzed during the mean follow-up period of 29 ± 13 months. The 3-years graft survival rate was calculated by Kaplan-Meyer method. At 100-200 ng/ml maintenance concentration (estimated by C0 concentration) the generic formulation was shown to yield significantly lower Cmax (824 vs 931 ng/ml respectively; p < 0,01) and AUC (3984 vs 4292 ng/ml/h respectively; p < 0,01). Acute rejection (biopsy-proven) rate proved considerably higher in generic Cy-A than in Neoral group (10,6% vs 4,1% respectively; p < 0,05). Chronic allograft dysfunction occurred in 14% of patients subjected to Neoral immunosuppression and in 24% of generic Cy-A recipients (p < 0,05). 3-years graft survival equaled 90 and 96% in generic Cy-A and Neoral groups, respectively (p = 0,05). Conclusion: Pharmacokinetic studies have shown the absorption profile of generic formulations to differ significantly from that of Neoral. Retrospective trial demonstrated higher acute rejection and chronic allograft dysfunction rates as well as lower 3-years graft survival in patients treated with generics and compared to Neoral group participants.
About the Author
E. S. Stoliarevich
ГУ НИИ трансплантологии и искусственных органов МЗ РФ, г. Москва
Russian Federation
Russian Federation
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For citations:
Stoliarevich E.S. Pharmacokinetic characteristics and clinical efficacy of generic cyclosporine formulations compared to Sandimmune Neoral. Nephrology and Dialysis. 2006;8(2):141-146. (In Russ.)
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