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


METHODS
This was an open-label, multicenter study with a single sequence, four-period crossover design. Eligible patients were 18 to 65 years of age, >6 months posttransplant with stable renal and hepatic function and receiving stable doses of Prograf twice a day for >2 weeks prior to enrollment. Patients received Prograf twice a day on days 1 to 14 and 29 to 42. Patients were converted to the same milligram-for-milligram daily dose of MR once daily on days 15 to 28 and 43 to 56. Twenty-four-hour PK profiles were obtained on days 14, 28, 42, and 56. Laboratory and safety parameters were also evaluated.


RESULTS
Of 70 patients, 62 completed all four PK profiles. The AUC0-24 of tacrolimus was comparable for Prograf twice a day (days 14 and 42) and MR tacrolimus once daily (days 28 and 56). The 90% confidence intervals for MR tacrolimus versus Prograf at steady state (days 28 and 56 vs days 14 and 42) was 0.85 to 0.92 for AUC0-24. MR tacrolimus was well tolerated with a safety profile comparable to that of Prograf. AUC0-24 was highly correlated to Cmin for Prograf (day 14, r = .93; Day 42, r = .89) and for MR tacrolimus (day 28, r = .93; day 56, r = .92). Renal and liver function remained stable. One patient experienced acute rejection.


CONCLUSIONS
The steady-state tacrolimus exposure of MR tacrolimus once daily is equivalent to Prograf twice a day after a milligram-for-milligram conversion in stable liver transplant recipients.
Florman
S
S
Tulane University, New Oreleans, Louisiana 70112, USA. sflorman@tulane.edu
Alloway
R
R
Kalayoglu
M
M
Lake
K
K
Bak
T
T
Klein
A
A
Klintmalm
G
G
Busque
S
S
Brandenhagen
D
D
Lake
J
J
Wisemandle
K
K
Fitzsimmons
W
W
First
M R
MR
D019540:Area Under Curve; D018592:Cross-Over Studies; D003692:Delayed-Action Preparations; D004334:Drug Administration Schedule; D006801:Humans; D007166:Immunosuppressive Agents / Q000008:administration & dosage* / Q000493:pharmacokinetics / Q000627:therapeutic use; D016031:Liver Transplantation / Q000276:immunology*; D008657:Metabolic Clearance Rate; D016559:Tacrolimus / Q000008:administration & dosage* / Q000493:pharmacokinetics / Q000627:therapeutic use
D003692:Delayed-Action Preparations; D007166:Immunosuppressive Agents; D016559:Tacrolimus