Comparison of two cyclosporine formulations in healthy volunteers: bioequivalence of the new Sang-35 formulation and Neoral.
This study was conducted to establish bioequivalence between a newly developed oral cyclosporine formulation, Sang-35 (SangStat Medical Corp., Menlo Park, CA), and the microemulsion formulation Neoral (Novartis Pharmaceuticals, East Hanover, NJ). In a randomized, open-label, two-way crossover study, 36 fasted, healthy male volunteers received a single 500-mg cyclosporine dose formulated either as Sang-35 or Neoral. Mean are under the concentration-time curve to infinity (AUC0-infinity) for Sang-35 was 13,900 microg x hr/L compared with 14,000 microg x hr/L for Neoral, with a 90% confidence interval (CI) of 96% to 103% for the geometric mean ratio of the two formulations. Mean maximum concentration (Cmax) was 1,690 microg/L for Sang-35 and 1,700 microg/L for Neoral, with a 90% CI of 96% to 103%. Geometric mean ratios for both AUC0-infinity and Cmax were within the acceptance criteria for bioequivalence (80-125%). Additional studies showed no differences between Sang-35 and Neoral after high-fat meals (n = 19), in female volunteers (n = 25) and in black volunteers (n = 7). It is concluded that single doses of the oral cyclosporine formulations Sang-35 and Neoral are bioequivalent in healthy fasted subjects, after high-fat meals, in women, and in blacks.
Schroeder
T J
TJ
SangStat Medical Corporation, Menlo Park, California 94025, USA.
Cho
M J
MJ
Pollack
G M
GM
Floc'h
R
R
Moran
H B
HB
Levy
R
R
Moore
L W
LW
Pouletty
P
P
D000284:Administration, Oral; D000328:Adult; D019540:Area Under Curve; D002626:Chemistry, Pharmaceutical; D018592:Cross-Over Studies; D016572:Cyclosporine / Q000008:administration & dosage / Q000493:pharmacokinetics*; D004334:Drug Administration Schedule; D005260:Female; D006801:Humans; D007166:Immunosuppressive Agents / Q000008:administration & dosage / Q000493:pharmacokinetics*; D008297:Male; D008875:Middle Aged; D013810:Therapeutic Equivalency
D007166:Immunosuppressive Agents; D016572:Cyclosporine