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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 p...

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Autores principales: Undre, Nasrullah, Baccarani, Umberto, Britz, Russel, Popescu, Irinel
Formato: Online Artículo Texto
Lenguaje:English
Publicado: International Scientific Literature, Inc. 2019
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6534968/
https://www.ncbi.nlm.nih.gov/pubmed/31086126
http://dx.doi.org/10.12659/AOT.909693
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author Undre, Nasrullah
Baccarani, Umberto
Britz, Russel
Popescu, Irinel
author_facet Undre, Nasrullah
Baccarani, Umberto
Britz, Russel
Popescu, Irinel
author_sort Undre, Nasrullah
collection PubMed
description 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.
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spelling pubmed-65349682019-07-29 Pharmacokinetic Profile of Prolonged-Release Tacrolimus When Administered via Nasogastric Tube in De Novo Liver Transplantation: A Sub-Study of the DIAMOND Trial Undre, Nasrullah Baccarani, Umberto Britz, Russel Popescu, Irinel Ann Transplant Original Paper 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. International Scientific Literature, Inc. 2019-05-14 /pmc/articles/PMC6534968/ /pubmed/31086126 http://dx.doi.org/10.12659/AOT.909693 Text en © Ann Transplant, 2019 This work is licensed under Creative Common Attribution-NonCommercial-NoDerivatives 4.0 International (CC BY-NC-ND 4.0 (https://creativecommons.org/licenses/by-nc-nd/4.0/) )
spellingShingle Original Paper
Undre, Nasrullah
Baccarani, Umberto
Britz, Russel
Popescu, Irinel
Pharmacokinetic Profile of Prolonged-Release Tacrolimus When Administered via Nasogastric Tube in De Novo Liver Transplantation: A Sub-Study of the DIAMOND Trial
title Pharmacokinetic Profile of Prolonged-Release Tacrolimus When Administered via Nasogastric Tube in De Novo Liver Transplantation: A Sub-Study of the DIAMOND Trial
title_full Pharmacokinetic Profile of Prolonged-Release Tacrolimus When Administered via Nasogastric Tube in De Novo Liver Transplantation: A Sub-Study of the DIAMOND Trial
title_fullStr Pharmacokinetic Profile of Prolonged-Release Tacrolimus When Administered via Nasogastric Tube in De Novo Liver Transplantation: A Sub-Study of the DIAMOND Trial
title_full_unstemmed Pharmacokinetic Profile of Prolonged-Release Tacrolimus When Administered via Nasogastric Tube in De Novo Liver Transplantation: A Sub-Study of the DIAMOND Trial
title_short Pharmacokinetic Profile of Prolonged-Release Tacrolimus When Administered via Nasogastric Tube in De Novo Liver Transplantation: A Sub-Study of the DIAMOND Trial
title_sort pharmacokinetic profile of prolonged-release tacrolimus when administered via nasogastric tube in de novo liver transplantation: a sub-study of the diamond trial
topic Original Paper
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6534968/
https://www.ncbi.nlm.nih.gov/pubmed/31086126
http://dx.doi.org/10.12659/AOT.909693
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