Clinical Pharmacokinetics of Oral Versus Sublingual Administration of Tacrolimus in Adult Liver Transplant Recipients

Abstract

Objectives: Oral tacrolimus administration is the common route of drug delivery. Recent studies suggest sublingual administration of tacrolimus as an alternative route may produce comparable drug trough levels with similar or even lower doses than the oral route, especially in lung transplant recipients; however, most of this research does not encompass intraindividual variations compared between the 2 routes. This study sought to compare the bioavailability and blood trough concentrations of orally and sublingually administered tacrolimus in adult liver transplant recipients by considering intraindividual variations in tacrolimus pharmacokinetics properties. Materials and Methods: Six adult liver transplant recipients received their tacrolimus either orally or sublingually within 2 consecutive days. Blood samples to determine tacrolimus concentrations were gathered at 0, 0.5, 1, 2, 4, 6, and 12 hours after oral and sublingual tacrolimus administration. Mean data values were used to calculate the pharmacokinetics parameters via the feathering or residual method, using the 1-compartment, firstorder elimination pharmacokinetics model. Compared pharmacokinetics parameters included drug bioavailability, maximum blood concentration (C max ), time to reach maximum blood level (T max ), and trough blood concentrations . Results: Trough whole blood levels, area under the concentration-time curve, T max , and C max after oral and sublingual administration of tacrolimus were not significantly different (10.4 ± 7.4 vs 11.2 ± 11.3 ng/mL for trough blood concentration, 181.5 ± 114.1 vs 160.8 ± 115.9 ng.h/mL for AUC, 1.9 ± 1.2 vs 1.4 ± 0.7 h for T max , and 19.9 ± 10.8 vs 17.2 ± 11.7 ng/mL for C max ). A double-peak phenomenon was observed in some concentrationtime profiles. Conclusions: Sublingual tacrolimus administration does provide therapeutic drug concentrations in adult liver transplant recipients. Therefore, sublingual tacrolimus may confidently be considered as an alternative route to oral administration in patients who are unable to swallow their drugs.

Sublingual tacrolimus as an alternative to oral administration for solid organ transplant recipients

“…While all of the previous reports described the administration of the contents of tacrolimus capsules, one study used a 1-mg/mL tacrolimus suspension administered drop by drop over a period of 10 minutes. 29 Conversion between enteral and sublingual administration of tacrolimus suspension in 6 adult liver transplant recipients resulted in mean trough concentrations and AUCs that did not differ significantly between the two routes (trough concentrations of 11.2 ± 11.3 ng/mL versus 10.4 ± 7.4 ng/mL for enteral and sublingual routes, respectively [p = 0.37], and AUCs of 160.8 ± 115.9 ng · hr/mL versus 181.5 ± 114.1 ng · hr/mL for enteral and sublingual routes, respectively [p = 0.19]). Overall, the pharmacokinetic parameters of tacrolimus were highly variable in this study.…”

“…Overall, the pharmacokinetic parameters of tacrolimus were highly variable in this study. 29 Tacrolimus is considered a hazardous drug and, if administered in any form other than intact capsules, requires special labeling, handling, and disposal (Table 2). 30 …”

Sublingual Administration of Tacrolimus: Current Trends and Available Evidence

“…One report compared the bioavailability and trough concentrations (C trough ) of oral and sublingual tacrolimus in six clinically stable adult liver transplant recipients in a prospective crossover design. No significant differences were seen between oral and sublingual tacrolimus with regard to C trough , T max , C max , or AUC.…”

Impact of Molecular Adsorbent Recirculating System Therapy on Tacrolimus Elimination: A Case Report

“…Current tacrolimus pharmacokinetic data suggest complete absorption and achievement of peak concentrations 3 hours after administration of an oral immediate release dose [4,10]. As such, an initial tacrolimus blood level was drawn !3 hours after an oral dose.…”