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Sublingual tacrolimus administration provides similar drug exposure to per‐oral route employing lower doses in liver transplantation: a pilot study

2017; Wiley; Volume: 45; Issue: 9 Linguagem: Inglês

10.1111/apt.14022

1365-2036

Sandra Solari, Alejandra Cancino, Rodrigo Wolff, Blanca Norero, José Ignacio Vargas, Francisco Barrera, Juan Francisco Guerra, Jorge Martínez, Nicolás Jarufe, Alejandro Soza, Marco Arrese, Carlos Benítez,

Transplantation: Methods and Outcomes

Summary Background Per‐oral tacrolimus administration is not always practicable. Sublingual administration is a potential alternative, but its feasibility and effectiveness compared with oral route has not been established. Aim To compare tacrolimus drug exposure after sublingual and oral administration in liver transplant recipients. Methods Experimental, open‐label, non‐randomised, cross‐over study. Tacrolimus exposure was evaluated in 32 liver transplant recipients receiving oral administration. 12 h tacrolimus area‐under‐the‐curve ( AUC 0–12 h ) was calculated using tacrolimus blood concentrations at 0‐0.5‐1‐2‐4‐6‐8‐12 hrs post‐dose. Recipients were switched to sublingual administration, and dose was adjusted to reach similar trough levels, new AUC 0‐12 h was calculated. Correlation between AUC 0‐12 h and trough levels was determined for both oral and sublingual phases. Results Similar trough levels were accomplished with oral and sublingual administration (6.68 ± 2 ng/mL vs. 6.62 ± 1.9 ng/mL ( P = 0.8)). Although concentration 2 h post dose was higher in oral phase (15.36 ± 7.14 vs. 13.18 ± 5.64, P = 0.015), AUC 0‐12 h was similar in both phases (116.6 ± 34.6 vs. 111.5 ± 36.93 ng/mL * h, P = 0.19). Daily dose of tacrolimus required in sublingual phase was 37% lower than that used in oral phase ( P < 0.0001), suggesting significantly increased bioavailability of tacrolimus when employing sublingual route. Good correlation between AUC 0‐12 h and trough levels was observed in sublingual phase ( r 2 = 0.74). Twenty‐two recipients were maintained on sublingual administration after the end of study (mean follow‐up: 18.7 ± 5.8 months). No difference in liver function tests or rejection rates was found during follow‐up period. Conclusions Sublingual administration of tacrolimus is feasible and provides similar drug exposure compared with oral administration. In our study, at long‐term follow‐up, sublingual administration was not associated with liver transplant rejection.