Assessment of the Bioequivalence of a Generic Cyclosporine A by a Randomized Controlled Trial in Stable Renal Recipients

Background. The aim of this study was to determine the bioequivalence of Cysporin, a generic cyclosporine A, compared with Neoral in stable renal transplant recipients. Methods. Study design consisted of an open label, two-way crossover, randomized controlled trial of Cysporin versus Neoral in stable renal transplant recipients. In all, 33 patients were enrolled; 31 were randomized and 28 were evaluable. AUCs 0–12 were done on day 14 and 28; C0 and C2 were done on days 0, 7, 21 and 35. Dose conversion was 1:1. Outcome measures for serum cyclosporin A concentrations expressed as the mean±SD were AUC 0–12 (μg.hr/L), Cmax (μg/L), C2 (μg/L), Tmax (hr) and T1/2 (hr). Mean and 90% CI of the ratio Cysporin/Neoral of log-transformed data were calculated using a general linear model. Results. The main pharmacokinetic features were: AUC0–12: Cysporin 3495±1319, Neoral 3853±1378 (P<0.05); Cmax: Cysporin 755±301, Neoral 881±368 (P<0.05); C2: Cysporin 613±235, Neoral 672±255 (P>0.05); Tmax: Cysporin 1.9±0.8, Neoral 1.4±0.6 (P<0.005); and T1/2: Cysporin 8.8±4.3, Neoral 8.7±6.2 (P>0.05). Estimated ratios of Cysporin/Neoral were: AUC 0.93 (90% CI 0.88–0.98; P<0.05); Cmax 0.88 (90% CI 0.80–0.97; P<0.05); and Tmax 1.32 (90% CI 1.14–1.53; P<0.005). Conclusions. Both the extent and rate of absorption of Cysporin are significantly less than those of Neoral. The 90% CI for the ratios of Cysporin/Neoral for AUC and Cmax lie within 0.80–1.25. Hence in this clinical context Cysporin is pharmacologically bioequivalent with Neoral. This study illustrates the importance of testing bioequivalence of generic cyclosporine A products in transplant recipients not healthy volunteers.