Conversion of stable renal allograft recipients to a bioequivalent cyclosporine formulation.
BACKGROUND
Gengraf capsule, an AB-rated generic cyclosporine for Neoral, has been shown to be bioequivalent in previous studies. The purpose of this pharmacokinetic study performed in stable renal transplant recipients was to evaluate interchangeability of Gengraf and Neoral.


METHODS
Using an open-label, three-period design, 50 renal transplant recipients taking stable doses of Neoral completed a multicenter study. Subjects continued their Neoral regimen during period I (days 1-14). Subjects then switched from Neoral on a milligram-for-milligram basis to Gengraf during period II (days 15-28), followed by conversion to the same milligram-for-milligram dosing regimen of Neoral during period III (days 29-35). Twelve-hour pharmacokinetic evaluations (maximum observed blood concentration [C(max) ], concentration before dosing [C(trough) ], time to maximum observed concentration [T(max) ], and area under the blood concentration-vs.-time curve [AUC]) occurred on days 1, 14, 15, 28, and 29. Additional predose samples (C (trough)) were evaluated on days 7, 21, and 35. Laboratory and safety parameters were also evaluated.


RESULTS
The pharmacokinetics of Gengraf (C(max), T(max), C(trough), and AUC) were indistinguishable from the Neoral values in stable renal allograft recipients. The bioequivalent capsules were interchangeable with respect to C(max), C(trough), and AUC at steady state and also on conversion from one capsule formulation to the other. The 90% confidence intervals (CI) for the Gengraf versus Neoral comparison at steady state (day 28 vs. day 14) were 0.95 to 1.03 for AUC and 0.92 to 1.04 for C(max). Trough concentrations remained consistent throughout the study, with no need for dosage adjustment in any of the subjects. Gengraf is well tolerated, with an excellent safety profile, comparable to the safety profile of Neoral. CONCLUSIONS The pharmacokinetics of Gengraf are equivalent and indistinguishable from those of Neoral. Gengraf is well tolerated and interchangeable with Neoral in stable renal transplant recipients.
Roza
Allan
A
Department of Surgery, Medical College of Wisconsin, Milwaukee, WI 53226, USA. aroza@mcw.edu.
Tomlanovich
Stephen
S
Merion
Robert
R
Pollak
Raymond
R
Wright
Francis
F
Rajagopalan
P
P
Pruett
Timothy
T
Scandling
John
J
Ryan
Joan
J
Awni
Walid
W
Schweitzer
Sarah
S
Greco
Renee
R
Lam
Wayne
W
Nabulsi
Azmi
A
Hoffman
Rebecca
R
D000328:Adult; D000368:Aged; D016572:Cyclosporine / Q000009:adverse effects / Q000493:pharmacokinetics / Q000627:therapeutic use; D016568:Drugs, Generic / Q000009:adverse effects / Q000493:pharmacokinetics / Q000627:therapeutic use; D005260:Female; D006801:Humans; D007166:Immunosuppressive Agents / Q000009:adverse effects / Q000493:pharmacokinetics* / Q000627:therapeutic use*; D016030:Kidney Transplantation; D008297:Male; D008875:Middle Aged; D019233:Retreatment; D012449:Safety; D013810:Therapeutic Equivalency
D016568:Drugs, Generic; D007166:Immunosuppressive Agents; D016572:Cyclosporine