Pharmacokinetics of a new oral formulation of cyclosporine in liver transplant recipients.
Trough concentrations of cyclosporine can be highly variable because of its poor bioavailability in current oral formulations, Sandimmune (SIM). Neoral (N-SIM) a new microemulsion of cyclosporine is more readily absorbed than SIM in healthy controls. The present study compared the pharmacokinetic profiles of SIM and N-SIM following orthotopic liver transplantation. In 16 patients with partial biliary diversion, 1 week after transplantation, the bioavailability and peak concentration of a single 300 mg dose of N-SIM were greater than SIM by 724% (p = 0.0019) and 800% (p = 0.0001), respectively. In 39 patients who were on stable doses of cyclosporine 1 month after transplantation, the bioavailability of N-SIM was higher than that of SIM under both fasting (+64%, p = 0.001) and fed (+37%, p = 0.004) conditions. Trough concentrations were similar for the two formulations. However, peak concentrations were higher for N-SIM in both fasting (+119%, p = 0.003) and fed (+53%, p = 0.003) patients. Also, time to peak was shorter for N-SIM in both fasting (-21%, p = 0.027) and fed (-59%, p = 0.0001) patients. The correlation between trough concentrations and bioavailability was greater for N-SIM than for SIM in fasted (r = 0.80, p = 0.0001 versus r = 0.75, p = 0.0001) and fed patients (r = 0.65; p = 0.002 versus r = 0.55; p = 0.012). We conclude that the rate of absorption and the bioavailability of N-SIM is significantly and consistently better than SIM and may, therefore, improve the therapeutic index of cyclosporine after liver transplantation.
Freeman
D
D
Faculty of Medicine, University of Western Ontario, London, Canada.
Grant
D
D
Levy
G
G
Rochon
J
J
Wong
P Y
PY
Altraif
I
I
Asfar
S
S
D000284:Administration, Oral; D001682:Biological Availability; D016572:Cyclosporine / Q000008:administration & dosage / Q000493:pharmacokinetics*; D004655:Emulsions; D005260:Female; D006801:Humans; D016031:Liver Transplantation; D008297:Male; D008875:Middle Aged
D004655:Emulsions; D016572:Cyclosporine