During a research program, SangStat Medical Corporation developed more than
270 oral cyclosporine formulations. On the basis of animal and clinical tr
ials, 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 c
yclosporine doses of Sang-35 (AUC(0-infinity): 13 900 +/- 2470 mu g . h L-1
, mean +/- standard deviation (SD)) and of Neoral (AUC(0-infinity): 14000 /- 2900 mu g . h . L-1) resulted in equal areas-under-the-time-concentratio
n curve (AUC(0-infinity)). Sang-35 and Neoral were also bioequivalent in he
althy male subjects after high-fat meals as well as in female and African-A
merican subjects. In stable kidney transplant patients (n = 12) receiving a
mean (+/- SD) cyclosporine dose of mg/d (3.6 +/- 1.6 mg/ kg/d), AUC(0-12 h
) after Sang-35 was, as expected, significantly higher than that after Sand
immune (4550 +/- 1858 vs 3468 +/- 1402 mu g . h . L-1, p < 0.01). Sang-35 a
nd Neoral resulted in equivalent cyclosporine AUC(0-12 h) values (4120 +/-
1508 and 4377 +/- 1579 mu g . h . L-1, respectively) in stable kidney trans
plant 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 San
dimmune to Sang-35. Based on a conversion strategy targeting AUC equivalenc
e, 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 tolerab
ility profiles. It is concluded that Sang-35 and Neoral are bioequivalent a
nd that patients can safely and easily be switched from Neoral or, in combi
nation with dose adjustment, from Sandimmune to Sang-35.