Further elucidation on the effect of food on the pharmacokinetics of trientine.

PURPOSE: Trientine dihydrochloride (TETA-2HCl) – a copper-selective chelator that forms a stable soluble complex with copper (Cu) and promotes excretion of this complex via the urine – is used as a treatment in Wilson Disease (WD) patients who are intolerant to D-penicillamine. Although in clinical practice patients are instructed to take TETA-2HCl on an empty stomach at least one hour before meals or two hours after meals, the effect of food on the pharmacokinetics of TETA-2HCl has not previously been systematically investigated in humans. METHODS: In this open-label, single dose, randomized, two period cross-over study in healthy adults, a single oral dose of 600 mg of TETA-2HCl (2 × 300 mg capsules) was once administered under fed and once under fasted conditions with a wash-out period of at least one week. Blood samples were collected for up to 48 h after each dosing for analysis of plasma trientine (TETA) and its metabolites N1-acetyltriethylenetetramine (MAT) and N1-N10-diacetyltriethylenetetramine (DAT). RESULTS: Food had a significant effect on the pharmacokinetics of TETA and its metabolites MAT and DAT. Maximum plasma concentrations, and the exposures of TETA are significantly reduced by food (Cmax: 45%, AUC0 − t and AUC0 − inf: 44%.). Similar effects were seen for the metabolites MAT and DAT. The tolerability of treatment with TETA-2HCl was not affected by the intake of food. CONCLUSION: The study shows a significant impact of food on the pharmacokinetics of TETA, supporting the current instruction on administration of TETA-2HCl on an empty stomach in clinical practice. ClinicalTrials.gov Identifier: EudraCT number: 2018-001982-17. Date registered: 16 May 2018.