Pharmacokinetic Profile of Prolonged-Release Tacrolimus When Administered via Nasogastric Tube in De Novo Liver Transplantation: A Sub-Study of the DIAMOND Trial.
Undre, N., Baccarani, U. et al. (2019).Annals of Transplantation; 14(24): 268-272.
Aims
This sub-study of the DIAMOND trial aimed to assess the absorption and pharmacokinetic profile of prolonged-release tacrolimus when administered by nasogastric tube immediately post-transplant.
Interventions
Patients were randomized to 1 of 3 study arms (1: 1: 1) to receive prolonged-release tacrolimus. In Arms 1 and 2, patients received prolonged- release tacrolimus at an initial dose of 0.2 mg/kg/day and 0.15–0.175 mg/kg/day on Day 1 post-transplant, respectively, while in Arm 3 tacrolimus initiation at a dose of 0.2 mg/kg/day was delayed until Day 5 post-transplant. All patients received MMF and 1 bolus of corticosteroid, and patients in Arms 2 and 3 also received basiliximab.
Participants
10 de novo liver transplant recipients from the DIAMOND study.
Outcomes
Pharmacokinetic profile was measured using area under the concentration–time curve from 0 to 24 hours post-tacrolimus dose (AUC0–24), maximum observed concentration of tacrolimus (Cmax), time to Cmax (Tmax), minimum observed concentration of tacrolimus at 24-h post-dose (Cmin), and dose and body weight normalized AUC0–24, Cmax, and Cmin.
Follow-up
3 days
CET Conclusions
The DIAMOND study was a randomized controlled trial investigating the use of prolonged-release tacrolimus in liver transplant recipients. This small sub-study looks at the pharmacokinetics of prolonged-release tacrolimus delivered as a suspension via a nasogastric tube. The authors demonstrate that by day 3 post-transplant, AUC increases and variability reduces, presumably as gut motility returns. The authors conclude that delivery via nasogastric tube is safe and equivalent to oral administration in these patients. However, there is no comparison group (using intact capsules taken orally), so equivalence is only inferred from the results reported in previous manuscripts. Sample size is small (just 10 patients), so a formal prospective comparison would be required to confirm these conclusions.
Data analysis
Modified intention-to-treat analysis
Trial registration
ClinicalTrials.gov - NCT01011205