Determining Equivalence Dose for Oral Versus Sublingual Administration of Tacrolimus in Hepatic Receptors

Summary

After liver transplantation one of the most important cost, for both patients and their health insurance system, is immunosuppressive drug therapy. Tacrolimus (FK 506) is considered the cornerstone of immunosuppressive therapy in solid organ transplantation. Oral administration is the usual route, however, sublingual (SL) administration has been recently reported. This method of administration avoids first pass metabolism and allows an alternative route after transplant surgery, particularly in those patients who should extend the period of fasting (prolonged intubation, ileus, etc). Interestingly, in some studies, the dose of tacrolimus SL required to maintain similar plasma concentrations compared with oral administration, is significantly lower, even up to 50%, which can result in considerable savings in short and long term. Among these studies, only one was conducted in liver recipients. This study suggest that SL administration of tacrolimus could allow to obtain similar concentrations compared with oral administration. The design of this study did not assess the existence of differences in the dose required and only included six patients.

Timeline

Start

2015-03

Primary completion

2016-03

Completion

2016-03

Publications

• Results Agopian VG, Petrowsky H, Kaldas FM, Zarrinpar A, Farmer DG, Yersiz H, Holt C, Harlander-Locke M, Hong JC, Rana AR, Venick R, McDiarmid SV, Goldstein LI, Durazo F, Saab S, Han S, Xia V, Hiatt JR, Busuttil RW. The evolution of liver transplantation during 3 decades: analysis of 5347 consecutive liver transplants at a single center. Ann Surg. 2013 Sep;258(3):409-21. doi: 10.1097/SLA.0b013e3182a15db4.
• Results Rabkin JM, Corless CL, Rosen HR, Olyaei AJ. Pharmacoeconomic study of tacrolimus-based versus cyclosporine-based immunosuppressive therapy following liver transplantation. Transplant Proc. 2001 Feb-Mar;33(1-2):1532-4. doi: 10.1016/s0041-1345(00)02585-9. No abstract available.
• Results Collin C, Boussaud V, Lefeuvre S, Amrein C, Glouzman AS, Havard L, Billaud EM, Guillemain R. Sublingual tacrolimus as an alternative to intravenous route in patients with thoracic transplant: a retrospective study. Transplant Proc. 2010 Dec;42(10):4331-7. doi: 10.1016/j.transproceed.2010.09.126.
• Results Reams BD, Palmer SM. Sublingual tacrolimus for immunosuppression in lung transplantation: a potentially important therapeutic option in cystic fibrosis. Am J Respir Med. 2002;1(2):91-8. doi: 10.1007/BF03256598.
• Results Reams D, Rea J, Davis D, Palmer S. Utility of sublingual tacrolimus in cystic fibrosis patients after lung transplantation. J Heart Lung Transplant. 2001 Feb;20(2):207-208. doi: 10.1016/s1053-2498(00)00447-2. No abstract available.
• Results Romero I, Jimenez C, Gil F, Escuin F, Ramirez E, Fudio S, Borobia A, Carcas A. Sublingual administration of tacrolimus in a renal transplant patient. J Clin Pharm Ther. 2008 Feb;33(1):87-9. doi: 10.1111/j.1365-2710.2008.00884.x.
• Results Srinarong P, Pham BT, Holen M, van der Plas A, Schellekens RC, Hinrichs WL, Frijlink HW. Preparation and physicochemical evaluation of a new tacrolimus tablet formulation for sublingual administration. Drug Dev Ind Pharm. 2012 Apr;38(4):490-500. doi: 10.3109/03639045.2011.613075. Epub 2011 Sep 30.
• Results Tsapepas D, Saal S, Benkert S, Levine D, Delfin M, Cremers S, Amann S, Dadhania D, Kapur S, Aull M. Sublingual tacrolimus: a pharmacokinetic evaluation pilot study. Pharmacotherapy. 2013 Jan;33(1):31-7. doi: 10.1002/phar.1149.
• Results van de Plas A, Dackus J, Christiaans MH, Stolk LM, van Hooff JP, Neef C. A pilot study on sublingual administration of tacrolimus. Transpl Int. 2009 Mar;22(3):358-9. doi: 10.1111/j.1432-2277.2008.00779.x. Epub 2008 Oct 30. No abstract available.
• Results Watkins KD, Boettger RF, Hanger KM, Leard LE, Golden JA, Hoopes CW, Singer JP. Use of sublingual tacrolimus in lung transplant recipients. J Heart Lung Transplant. 2012 Feb;31(2):127-32. doi: 10.1016/j.healun.2011.10.015. Epub 2011 Dec 16.
• Results Nasiri-Toosi Z, Dashti-Khavidaki S, Nasiri-Toosi M, Khalili H, Jafarian A, Irajian H, Abdollahi A, Sadrai S. Clinical pharmacokinetics of oral versus sublingual administration of tacrolimus in adult liver transplant recipients. Exp Clin Transplant. 2012 Dec;10(6):586-91. doi: 10.6002/ect.2012.0032. Epub 2012 Jul 5.

Drugs

Indications

No indication recorded.