Therapeutic drug monitoring of modified release once daily tacrolimus in de novo renal transplant with conversion to a twice daily generic in the stable period

• Bellusci CP^1*,
• Rocco C¹,
• Aulicino P¹,
• Mecikovsky D¹,
• Curras V¹

1. ¹Hegoburu S, et al. Influence of MDR1 C1236T polymorphism on lopinavir plasma concentration and virological response in HIV‑1‑infected children. Gene 2013;522:96‑101. Therapeutic drug monitoring of modified release once daily tacrolimus in de novo renal transplant with conversion to a twice daily generic in the stable period Sir, Management of transplant patients is a challenge in developing countries in view of the availability of multiple generics and different formulations in the market and financial constraints faced by the patients. Advagraf® (Astellas Pharma US, Inc.) is available as a once daily modified release (MR) tacrolimus. Comparable clinical outcome, trough concentration and tacrolimus area under concentration time curve (AUC0–24) between twice a day, tacrolimus innovator (Prograf®) and tacrolimus MR in renal transplant recipients have been reported.[1] Studies used Prograf® as de novo and found a comparable AUC0–24 after patients were converted later to tacrolimus MR (Advagraf®).[2] In comparison to the conventional release formulation (Pangraf) of tacrolimus, the modified release formulation (Advagraf) is subject to wet granulation and capsule filling to delay drug release of tacrolimus.[3] PanGraf® (tacrolimus twice daily, generic) is widely prescribed and used successfully in this population from the advent of tacrolimus into the Indian market in 2005. The cost of 1 mg of tacrolimus is INR 100 for the innovator, Prograf® (Astellas Pharma US, Inc.) in comparison to INR 43 for PanGraf® (Panacea Biotec Ltd ., India). We wish to report an experience with therapeutic drug monitoring (TDM) of tacrolimus in four de novo renal transplant recipients who were initiated on Advagraf®, once daily prior to renal transplantation and subsequently converted to the twice daily, PanGraf® in the stable post transplant period. Patients (case no. 1, 2, 3 and 4) were initiated on Advagraf®, tacrolimus MR after giving written informed consent, two days prior to transplantation (dose between 0.192 and 0.202 mg/kg/day), along with prednisolone and mycophenolate mofetil. Patients (case no. 1, 3 and 4) were from the North east of India and case no. 2 was from the South of India. Whole blood concentration of tacrolimus was measured by the LC‑MS/MS. Reversed phase chromatography was performed using a.

Published in Journal of Pharmacology and Pharmacotherapeutics