Conversion of stable kidney transplant recipients from a twice daily Prograf-based regimen to a once daily modified release tacrolimus-based regimen.
Modified release (MR) tacrolimus is an extended release formulation administered once daily (qD). The purpose of this pharmacokinetic (PK) study was to evaluate tacrolimus exposure in stable kidney transplant recipients converted from Prograf twice a day to MR tacrolimus qD.


METHODS
This was an open-label, multicenter study with a crossover design. Eligible patients were 18 to 65 years of age, more than 6 months posttransplant with stable renal function, and received stable Prograf doses more than 2 weeks prior to enrollment. Patients received Prograf twice a day through day 7; 24-hour PK profiles were obtained on days 1 and 7. Patients were converted to the same milligram-for-milligram daily dose of MR tacrolimus qD in the morning on day 8; 24-hour PK profiles were obtained for MR tacrolimus on days 8, 14, and 21. Laboratory and safety parameters were also evaluated.


RESULTS
Most patients (67 of 70) completed all 5 PK profiles. The 90% confidence intervals (CI) for the MR tacrolimus vs Prograf comparison at steady state (days 14 and 21 vs days 1 and 7) were 90.7 and 99.4 for AUC0-24 and 82.7 and 91.9 for Cmin. MR tacrolimus was well tolerated with a safety profile comparable to that of Prograf. AUC0-24 was highly correlated to Cmin for Prograf (day 1, r = 0.80; day 7, r = 0.84) and MR tacrolimus (day 14, r = 0.92; day 21, r = 0.86). Renal function remained stable after conversion to MR tacrolimus.


CONCLUSIONS
The steady state PK of MR tacrolimus are equivalent to Prograf after a milligram-for-milligram conversion in stable kidney transplant recipients. The results provide evidence to support a safe 1:1 conversion from Prograf twice a day to MR tacrolimus.
Alloway
R
R
University of Cincinnati, College of Medicine, Cincinnati, Ohio 45267-0558, USA. rita.alloway@uc.edu
Steinberg
S
S
Khalil
K
K
Gourishankar
S
S
Miller
J
J
Norman
D
D
Hariharan
S
S
Pirsch
J
J
Matas
A
A
Zaltzman
J
J
Wisemandle
K
K
Fitzsimmons
W
W
First
M R
MR
D000328:Adult; D000368:Aged; D019540:Area Under Curve; D018592:Cross-Over Studies; D003692:Delayed-Action Preparations; D004334:Drug Administration Schedule; D004359:Drug Therapy, Combination; D006801:Humans; D007166:Immunosuppressive Agents / Q000008:administration & dosage / Q000493:pharmacokinetics / Q000627:therapeutic use; D016030:Kidney Transplantation / Q000276:immunology*; D008657:Metabolic Clearance Rate; D008875:Middle Aged; D016559:Tacrolimus / Q000008:administration & dosage* / Q000493:pharmacokinetics* / Q000627:therapeutic use
D003692:Delayed-Action Preparations; D007166:Immunosuppressive Agents; D016559:Tacrolimus