Determining the conversion ratios for oral versus sublingual administration of tacrolimus in solid organ transplant recipients

Abstract

Tacrolimus is utilized as maintenance immunosuppression in solid organ transplant (SOT). Current literature has reported conflicting conversion ratios when transitioning between oral and sublingual tacrolimus, and the exact conversion ratio has not been fully established in SOT. The purpose of this study was to determine the conversion ratios between oral and sublingual tacrolimus needed to achieve equivalent whole blood concentrations in heart, kidney, liver, and lung transplant recipients. A retrospective, single-center analysis was conducted at Mayo Clinic in Florida. One hundred and eighteen hospitalized SOT recipients who received oral and sublingual tacrolimus during the same inpatient admission from June 1, 2012, through June 1, 2017, were reviewed. The median conversion ratio of sublingual to oral tacrolimus was 1.34 (IQR: 1.03-1.93) in all SOT, 1.25 (IQR: 1.08-1.64) in heart transplant, 1.23 (IQR: 1.1-2.06) in kidney transplant, 1.64 (IQR: 1.27-2.29) in liver transplant, and 1.34 (IQR: 0.94-1.93) in lung transplant. A slightly higher dose of oral tacrolimus is needed in the majority of solid organ recipients in our population when converting between sublingual to oral tacrolimus administration. K E Y W O R D S

Development and Characterization of Tacrolimus Tablet Formulations for Sublingual Administration

“…the highly vascularised sublingual route of administration, may further improve the bioavailability of tacrolimus by circumventing the first-pass metabolism in the gut and liver. There are clinical studies to prove that sublingual tacrolimus is comparable to or more effective than oral administration, concerning bioavailability, in solid organ transplant patients [12][13][14].…”

Use of sublingual tacrolimus in adults undergoing hematopoietic cell transplant: A pilot study

“…Studies undertaken to determine the optimal SL to PO dose conversion ratio in solid organ transplant patients report variable results depending on the type of organ received, with most transplant centers recommending a ratio of 1 (1:1) or 0.5 (1:2). 3,7,8,[11][12][13] Unfortunately, most exclude patients on medications that interact with tacrolimus metabolism or fail to report that relevant information. Given that enteral and first-pass hepatic metabolism are bypassed with the SL route, one report suggests that a ratio of 1:1 be used when major drug interactions are present.…”