title: A prospective, multicenter study of once-daily extended-release tacrolimus in de novo liver transplant recipients.
abstract: To minimize noncompliance in organ transplantation, a new formulation was developed of once-daily extended-release (EXTD) tacrolimus. To analyze the efficacy and safety of this new drug formulation in de novo liver transplant recipients, a prospective, multicenter study was performed in six centers in Spain. The primary objective of the study was to evaluate the incidence of biopsy-proven acute rejection episodes (BPAR) according to the BANFF criteria during the first 3 months of immunosuppression with the EXTD formulation of tacrolimus. Fifty-two patients received a mean initial dose of 10.0 ± 3.8 mg that was gradually reduced to 7.1 ± 4.0 mg, achieving stable mean blood levels of 8.6 ± 3.7 ng/mL at 3 months. BPAR was reported in seven (13%) patients, but patient and graft survivals were 100%. After transplantation liver function improved and was stably maintained throughout the study. At 3 months, mean bilirubin levels were 2.1 ± 5.5 mg/dL and mean alanine aminotransferase and aspartate aminotransferase were 61.6 ± 75.2 U/L and 55.2 ± 76.9 U/L, respectively. Mean serum creatinine of 0.8 ± 0.3 mg/dL pretransplant increased to 1.1 ± 0.4 mg/dL after 3 months (P < .0001). There was no significant increase in the rate of hypertension from pretransplant levels: 30% at baseline versus 31% at 3 months. Mean glucose levels did not change significantly throughout the study. There were no cases of hepatitis C virus relapse. EXTD tacrolimus demonstrated excellent stability in blood trough levels with a good efficacy and safety profile in de novo liver transplant recipients that was similar to the well-described properties of standard-release twice-daily formulation of tacrolimus.
authors.affiliation: HBP Surgery and Transplants Department, Universidad Autónoma de Barcelona, Barcelona, Spain. rcharco@gmail.com
authors.forename: R
authors.initials: R
authors.lastname: Charco
authors.forename: M
authors.initials: M
authors.lastname: Caralt
authors.forename: L
authors.initials: L
authors.lastname: Lladó
authors.forename: A
authors.initials: A
authors.lastname: Valdivieso
authors.forename: J
authors.initials: J
authors.lastname: Fabregat
authors.forename: A
authors.initials: A
authors.lastname: Matarranz
authors.forename: I
authors.initials: I
authors.lastname: Gonzalez-Pinto
authors.forename: F
authors.initials: F
authors.lastname: Pardo
authors.forename: E
authors.initials: E
authors.lastname: Fábrega
authors.forename: I
authors.initials: I
authors.lastname: Bilbao
mesh_terms: D000410:Alanine Transaminase / Q000097:blood; D001219:Aspartate Aminotransferases / Q000097:blood; D001663:Bilirubin / Q000097:blood; D003692:Delayed-Action Preparations; D005260:Female; D006084:Graft Rejection; D006801:Humans; D007166:Immunosuppressive Agents / Q000008:administration & dosage*; D016031:Liver Transplantation; D008137:Longitudinal Studies; D008297:Male; D008875:Middle Aged; D011446:Prospective Studies; D016559:Tacrolimus / Q000008:administration & dosage*
chemical_list: D003692:Delayed-Action Preparations; D007166:Immunosuppressive Agents; D001219:Aspartate Aminotransferases; D000410:Alanine Transaminase; D001663:Bilirubin; D016559:Tacrolimus