Pharmacokinetic study of conversion from tacrolimus twice-daily to tacrolimus once-daily in stable lung transplantation.
BACKGROUND
Tacrolimus twice-daily (TAC BID) is widely used in lung transplantation (LT), but there are little data on the use of tacrolimus once-daily (TAC QD) in this population. The objective of this study was to compare the pharmacokinetics (PK) of TAC BID and TAC QD in stable, adult LT patients.


METHODS
Phase II, open-label, single-center, single-arm, prospective pilot PK study. Nineteen LT recipients with more than 6 months of postoperative follow-up and on TAC BID-based therapy were converted to TAC QD on a 1:1 (mg/mg) basis. Patients had been stable during the previous 3 months, and cystic fibrosis patients were excluded. One 24-hr PK profile was obtained on day -14 while patients were under TAC BID. A second PK profile was obtained 14 to 28 days after switching (day 0) to the same dose of TAC QD. Pre- and post-switch 24-hr PK profiles were compared.


RESULTS
Mean AUC0-24 hr was 279.8 ng mL/hr for TAC BID and 278.7 ng mL/hr for TAC QD (P=0.92). AUC0-12 hr of TAC BID was higher than the AUC12-24 hr. There was a good correlation between AUC0-24 hr and C24 for both QD (r=0.96) and BID (r=0.94) formulations. There were no differences in the adverse events occurring with the two formulations.


CONCLUSIONS
Tacrolimus bioavailability in steady state is similar in BID and QD formulations after conversion in stable LT recipients, excluding those with cystic fibrosis. Thus, our results indicate TAC BID can be safely switched to the more convenient QD formulation in this population.
1 Lung Transplantation Program, Servei de Pneumologia, Hospital Universitari Vall d'Hebron, Departament de Medicina, Universitat Autònoma de Barcelona, Barcelona, Spain. 2 CIBER de Enfermedades Respiratorias (CIBERES), Instituto de Salud Carlos III, Madrid, Spain. 3 Serveis Centrals de Laboratori, Secció de Farmacologia, Hospital Universitari Vall d'Hebron, Barcelona, Spain. 4 Address correspondence to: Alejandra Méndez, M.D., Lung Transplantation Program, Servei de Pneumologia, Hospital Universitari Vall d'Hebron, Departament de Medicina, Universitat Autònoma de Barcelona, Passeig Vall d'Hebron, 119-129, 08035 Barcelona, Spain.
Alejandra
A
Méndez
Cristina
C
Berastegui
Manuel
M
López-Meseguer
Víctor
V
Monforte
Carlos
C
Bravo
Albert
A
Blanco
Silvia
S
Camós
Leonor
L
Pou
Antonio
A
Roman
D000328:Adult; D019540:Area Under Curve; D001682:Biological Availability; D004334:Drug Administration Schedule; D005260:Female; D006801:Humans; D007166:Immunosuppressive Agents / Q000008:administration & dosage* / Q000493:pharmacokinetics*; D016040:Lung Transplantation / Q000379:methods*; D008297:Male; D008875:Middle Aged; D010865:Pilot Projects; D011446:Prospective Studies; D016559:Tacrolimus / Q000008:administration & dosage* / Q000493:pharmacokinetics*; D013997:Time Factors
D007166:Immunosuppressive Agents; D016559:Tacrolimus