Year: 1998
Type: article
Abstract: During a research program, SangStat Medical Corporation developed more than 270 oral cyclosporine formulations. On the basis of animal and clinical trials, Sang‐35 was chosen for clinical development, and bioequivalence with the cyclosporine microemulsion Neoral was established. In a cross‐over study involving 36 healthy male volunteers, single 500 mg cyclosporine doses of Sang‐35 (AUC0: 13900±2470 μg h L. mean ± standard deviation (SD)) and of Neoral (AUC0 14000 ± 2900 μg g.h L‐1) resulted in equal areas‐under‐the‐time‐concentration curve (AUC0‐∞). Sang‐35 and Neoral were also bioequivalent in healthy male subjects after high‐fat meals as well as in female and African‐American subjects. In stable kidney transplant patients (n = 12) receiving a mean (±SD) cyclosporine dose of mg/d (3.6 ± 1.6 mg/ kg/d), AUC0‐12 h after Sang‐35 was, as expected, significantly higher than that after Sandimmune (4550±858 vs 3468±1402 μg h L‐1, p<0.01). Sang‐35 and Neoral resulted in equivalent cyclosporine AUC0‐12 h h values (4120±1508 and 4377±1579 μg h L1, respectively) in stable kidney transplant patients (dose: 293±114 mg/d or 3.7±1.5 mg/kg/d, n = 32). In an additional study, 42 stable kidney graft patients were switched from Sandimmune to Sang‐35. Based on a conversion strategy targeting AUC equivalence, only one dose adjustment was required in 55% of the patients, and 95% of patients (40 of 42) needed three or fewer dose adjustments. The mean Sang‐35 dose was 7% lower than the mean Sandimmune dose. During the studies, Sang‐35 and Neoral exhibited similar safety and tolerability profiles. It is concluded that Sang‐35 and Neoral are bioequivalent and that patients can safely and easily be switched from Neoral or, in combination with dose adjustment, from Sandimmune to Sang‐35.
Source: Clinical Transplantation
Authors: M Roy First, Rita Alloway, Timothy J Schroeder
Language: English
Subfield: Transplantation
Field: Medicine
Domain: Health Sciences
Open Access status: bronze
OpenAlex ID: W4402988516