Therapeutic Drug Monitoring in De Novo Kidney Transplant Receiving the Modified-Release Once-Daily Tacrolimus M.L. Jelassi, S. Lefeuvre, A. Karras, L. Moulonguet, and E.M. Billaud ABSTRACT Introduction. Advagraf (AVF) a new formulation of tacrolimus (TRL), allows once-daily administration while showing similar efficacy and safety to the conventional Prograf (PGF), which is prescribed twice daily. Our study sought to compare short-term thera- peutic drug monitoring (TDM) of AVF and PGF in de novo kidney transplants. Patients and Methods. We retrospectively collected results of TDM performed on blood trough samples (C0) using an LC- MS/MS assay to quantify TRL exposure in the two groups. Twelve subjects received initial immunosuppression with AVF associated with mycophenolic acid, steroids, and immunoglobulins. We compared median doses and C0 levels with those obtained in 18 cases receiving an equivalent dose of PGF during the same period. Results and Discussion. Although both groups showed similar mean C0, the median dose in the AVF group tended to be higher than the PGF group—respectively, 9.8 and 7.9 mg/d—which may be attributed to the once-daily regimen, which inevitably results in lower C0 levels compared to the twice-a-day regimen, while overall exposure appeared similar in terms of area under the curve (AUC). This observation occured especially during the first weeks despite the extended release formulation. In fact, one patient who showed a low C0 (5.9 ng/mL) while receiving high doses of AVF (0.28 mg/kg), the AUC of 356 and 211 ng.h/mL performed on days 12 and 18 respectively showed exposure consistent with efficacy. Conclusion. In conclusion, it seemed to be necessary to use higher doses (25%) of Advagraf to reach the targeted C0 levels during the first weeks posttransplant. For patients who do not reach the targeted C0 despite high doses, TRL exposure should be assessed by AUC or peak levels (C4h). T ACROLIMUS (TRL), a well-established calcineurin inhibitor, is increasingly used to allograft rejection in solid organ and bone marrow transplantation. 1 Advagraf (AVF; Astellas Pharma Europe Ltd), a new modified- release (extended release) formulation of TRL, allows once-daily administration in the morning, 2 while showing a similar efficacy and safety profile as the conventional Prograf (PGF; Astellas Pharma Europe Ltd), which is prescribed twice daily. 3,4 Aside from sponsored clinical trials, 2,5 few data are available about AVF therapeutic drug monitoring (TDM) in clinical practice. Our study sought to compare short-term TDM between June 2007 and March 2010 of once-daily AVF with twice-daily PGF tacrolimus in de novo kidney transplant patients in our center. PATIENTS AND METHODS We retrospectively collected results of TDM performed on whole blood trough samples (C0) using an LC-MS/MS assay (Mass trak immunosuppressant kit, XE, RUO) to quantify TRL exposure in the two groups. Target therapeutic C0 were individually adapted From Pharmacology, AP-HP (M.L.J., S.L., E.M.B.) and Ne- phrology AP-HP (A.K.), Hôpital Européen G. Pompidou, Paris, Francé, Nephrology AP-HP (L.M.), Hôpital A Paré, Boulogne, France; Faculty of Pharmacy (M.L.J.), Monastir, Tunisia; and Paris Descartes university (S.L.), Paris, France. Address reprint requests to Dr E.M. Billaud, Laboratoire de Pharmacologie-Toxicologie, Hôpital Européen Georges Pompi- dou, 20 – 40, rue Leblanc, 75908 Paris, France. E-mail: eliane. billaud@egp.aphp.fr © 2011 Published by Elsevier Inc. 0041-1345/–see front matter 360 Park Avenue South, New York, NY 10010-1710 doi:10.1016/j.transproceed.2011.01.043 Transplantation Proceedings, 43, 491– 494 (2011) 491