Nonadherence is a critical issue in transplantation. Recently, Astellas designed a once-daily-extended release formulation of tacrolimus (Tac). Despite initial reports showing bioequivalence of Tac once-daily (Advagraf) with the original formulation requiring twice-daily intake (Tac twice-daily, Prograf), several groups have now shown a sustained decrease in Tac exposure upon conversion from Prograf to Advagraf. Here, we discuss the possible reasons for this observation and how it could affect the expected benefits of Advagraf, and we comment on the fact that a similar lack of bioequivalence might prevail with generic immunosuppressive drugs.
1Department of Nephrology, Clinique Universitaire Hôpital Erasme, Renal Transplantation Clinic, Brussels, Belgium.
2Department of Nephrology and Renal Transplantation, University Hospitals Leuven, Leuven, Leuven, Belgium.
The authors declare no funding or conflicts of interest.
Address correspondence to: Jean-Michel Hougardy, M.D., Ph.D., Department of Nephrology, Clinique Universitaire Hôpital Erasme, 808 Route de Lennik, B-1070 Bruxelles, Belgium. E-mail: firstname.lastname@example.org
J.M.H., H.d.J., D.K., and D.A. equally contributed in the writing of the manuscript.
Received 21 June 2011. Revision requested 11 July 2011.
Accepted 29 September 2011.