Pharmacokinetics of once- versus twice-daily tacrolimus formulations in kidney transplant patients receiving expanded criteria deceased donor organs: a single-center, randomized study.
BACKGROUND
Noncompliance to immunosuppressive treatment is 1 of the risk factors for kidney graft loss. The once-daily, prolonged-release tacrolimus formulation may improve treatment adherence. We sought to compare the pharmacokinetics of both tacrolimus formulations in older de novo recipients of a cadaveric renal transplant from an expanded-criteria donor.


METHODS
This randomized study included 27 patients (14 on once daily prolonged-release formulation [QD] and 13, on the twice-daily formulation [BID]), who were treated with 0.1 mg/kg per day of tacrolimus (target blood level, 5-8 ng/mL) mycophenolate mofetil prednisone and basiliximab induction.


RESULTS
At 24 hours, in combination with the blood levels were 4.70±2.50 versus 4.70±3.04 ng/mL (P=NS). There were no significant differences in the AUC0-24 of tacrolimus (QD/BID) at 3 days (300.8±60.15 vs 287.7±125.78 ng.h/mL) or 21 days (303.05±99.79 vs 275.26±75.37 ng.h/mL), nor in blood levels (ng/mL) at 1 month (8.76±2.46 vs 8.8±1.89), 3 months (7.30±1.72 vs 8.80±1.89) and 6 months (7.19±1.89 vs 6.60±1.71). At 3 days, there was a strong correlation between AUC0-24 and Cmin both for tacrolimus QD (r=.872) and BID (r = 1.0). The incidences of acute rejection episodes were: 0% versus 16.6%; graft survivals, 100% versus 92.3% (P=NS); and patient survivals, both 100%.


CONCLUSIONS
For older de novo recipients of kidneys from expanded criteria donors tacrolimus QD is comparable to the same dose in the BID formulation with similar at least short-term transplant outcomes.
Cabello
M
M
Nephrology, Services of Carlos Haya University Hospital, Malaga, Spain.
García
P
P
González-Molina
M
M
Díez de los Rios
M J
MJ
García-Sáiz
M
M
Gutiérrez
C
C
López
V
V
Sola
E
E
Burgos
D
D
Hernández
D
D
D000368:Aged; D000911:Antibodies, Monoclonal / Q000008:administration & dosage; D019540:Area Under Curve; D000077552:Basiliximab; D003692:Delayed-Action Preparations; D005260:Female; D006801:Humans; D007166:Immunosuppressive Agents / Q000008:administration & dosage / Q000493:pharmacokinetics*; D016030:Kidney Transplantation; D008297:Male; D008875:Middle Aged; D009173:Mycophenolic Acid / Q000008:administration & dosage / Q000031:analogs & derivatives; D011241:Prednisone / Q000008:administration & dosage; D011993:Recombinant Fusion Proteins / Q000008:administration & dosage; D016559:Tacrolimus / Q000008:administration & dosage / Q000493:pharmacokinetics*; D014019:Tissue Donors
D000911:Antibodies, Monoclonal; D003692:Delayed-Action Preparations; D007166:Immunosuppressive Agents; D011993:Recombinant Fusion Proteins; D000077552:Basiliximab; D009173:Mycophenolic Acid; D011241:Prednisone; D016559:Tacrolimus