RESUMO
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 (AUC0-12 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 AUC0-12 h was calculated. Correlation between AUC0-12 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), AUC0-12 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 AUC0-12 h and trough levels was observed in sublingual phase (r2 = 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.
Assuntos
Imunossupressores/administração & dosagem , Transplante de Fígado , Tacrolimo/administração & dosagem , Administração Oral , Administração Sublingual , Idoso , Disponibilidade Biológica , Estudos Cross-Over , Feminino , Humanos , Imunossupressores/sangue , Imunossupressores/farmacocinética , Imunossupressores/uso terapêutico , Masculino , Pessoa de Meia-Idade , Projetos Piloto , Tacrolimo/sangue , Tacrolimo/farmacocinética , Tacrolimo/uso terapêuticoRESUMO
Se presentan todos los casos que durante un periodo de 5 años, fueron remitidos de la consulta del autor y de primera vez, al estudio de gamagrafia del esofago por presentar sintomas relacionados con el reflujo gastroesofagico o para su diagnostico clinico. Se describen los resultados de 527 estudios gamagráficos y los parámetros por los cuales este trabajo permite clasificar los diferentes grados de severidad del reflujo, con lo que se define tambien el establecimiento de las distintas conductas terapeuticas en cada caso. Se analizan los 140 pacientes que durante este periodo y con dicha metodologia diagnostica y de seguimiento, requirieron la correccion quirurgica del reflujo gastroesofagico patologico y se evaluan los resultados gamagráficos y clinicos de la tecnica quirurgica utilizada.