Pharmacokinetic Profile of Prolonged-Release Tacrolimus When Administered via Nasogastric Tube in De Novo Liver Transplantation: A Sub-Study of the DIAMOND Trial

BACKGROUND: For patients unable to swallow during the immediate post-transplant period, immunosuppressant therapy may be initiated by administering prolonged-release tacrolimus as a suspension via a nasogastric tube. MATERIAL/METHODS: In this sub-study of the DIAMOND randomized controlled trial of prolonged-release tacrolimus in de novo liver transplant recipients, we investigated the pharmacokinetic (PK) profile of prolonged-release tacrolimus when administered via nasogastric tube immediately post-transplant. PK analyses were performed on whole-blood samples collected on Day 1 of tacrolimus administration and on Day 3 post-transplantation. Endpoints included AUC(0–24,) C(max), T(max), and C(min). RESULTS: In total, 10 patients were included in the PK sub-study. The overall mean daily dose of prolonged-release tacrolimus administered via nasogastric tube was higher on Day 1 (0.179 mg/kg) vs. Day 3 (0.140 mg/kg). Mean AUC(0–24) was higher and less variable on Day 3 vs. Day 1 (AUC(0–24) (coefficient of variation; CV): 301 (50.8) vs. 193 (94.5) ng·h/mL). Mean C(max) was lower and median T(max) was shorter on Day 1 vs. Day 3 (C(max) (CV): 15.1 (73.9) vs. 19.1 (47.9) ng/mL; T(max) (range): 2.0 (2.0–24.0) vs. 4.5 (0.5–24.0) h). A similar pattern was also observed when data were normalized for dose and body weight. CONCLUSIONS: In contrast to previously reported findings in healthy volunteers, nasogastric administration of prolonged-release tacrolimus suspension in liver transplant patients did not substantially affect the PK profile of tacrolimus vs. intact capsules. Nasogastric administration is thus a feasible option to ensure appropriate early tacrolimus exposure in de novo liver transplant recipients.