Wilson's Disease Treatment by Triethylene Tetramine Dihydrochloride (Trientine, 2HCI): Long-Term Observations

Morita, Jun; Yoshino, Makoto; Watari, Hiroshi; Yoshida, Ichiro; Motohiro, T; Yamashita, Fumio; Okano, Yoshiro; Hashimoto, Tsuyoshi

doi:10.1159/000457456

Cited by 18 publications

(11 citation statements)

References 5 publications

(7 reference statements)

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“…Trientine treatment has been linked to haematological abnormalities such as sideroblastic anaemia [20] and thrombocytopenia [6] in occasional patients under treatment for Wilson's disease, in whom it has also been reported to cause low serum iron without anaemia [21]. Drug-treated patients underwent modest but statistically significant decreases in haemoglobin, packed cell volume and erythrocyte numbers, which might signal an effect of drug treatment to lower Cu levels in the erythropoietic tissue.…”

Section: Discussionmentioning

confidence: 99%

A copper(II)-selective chelator ameliorates left-ventricular hypertrophy in type 2 diabetic patients: a randomised placebo-controlled study

et al. 2009

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Aims/hypothesis Cu(II)-selective chelation with trientine ameliorates cardiovascular and renal disease in a model of diabetes in rats. Here, we tested the hypothesis that Cu(II)-selective chelation might improve left ventricular hypertrophy (LVH) in type 2 diabetic patients. Methods We performed a 12 month randomised placebocontrolled study of the effects of treatment with the Cu (II)-selective chelator trientine (triethylenetetramine dihydrochloride, 600 mg given orally twice daily) on LVH in diabetic patients (n=15/group at baseline) in an outpatient setting wherein participants, caregivers and those assessing outcomes were blinded to group assignment. Using MRI, we measured left ventricular variables at baseline, and at months 6 and 12. The change from baseline in left ventricular mass indexed to body surface area (LVM bsa ) was the primary endpoint variable.Results Diabetic patients had LVH with preserved ejection fraction at baseline. Trientine treatment decreased LVM bsa by 5.0± 7.2 g/m 2 (mean ±SD) at month 6 (when 14 trientine-treated and 14 placebo-treated participants were analysed; p=0.0056 compared with placebo) and by 10.6± 7.6 g/m 2 at month 12 (when nine trientine-treated and 13 placebo-treated participants were analysed; p=0.0088), whereas LVM bsa was unchanged by placebo treatment. In a multiple-regression model that explained~75% of variation (R 2 =0.748, p=0.001), cumulative urinary Cu excretion over 12 months was positively associated with trientine-evoked decreases in LVM bsa . Conclusions/interpretation Cu(II)-selective chelation merits further exploration as a potential pharmacotherapy for diabetic heart disease.

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Section: Discussionmentioning

confidence: 99%

A copper(II)-selective chelator ameliorates left-ventricular hypertrophy in type 2 diabetic patients: a randomised placebo-controlled study

et al. 2009

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“…A total of 14 studies were identified [2,3,5,9,11,13,15,[18][19][20][21][23][24][25]. These are summarised in Table 4.…”

Section: Discussion and Review Of The Literaturementioning

confidence: 99%

Triethylene tetramine dihydrochloride (trientine) in children with Wilson disease: experience at King’s College Hospital and review of the literature

2008

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Our aim was to review our experience of trientine as chelation therapy in children with Wilson disease (WD) and compare to that reported in the literature. We made a retrospective review of the medical notes of 16 of 96 (17%) children diagnosed with WD between 1981 and 2006. Children were 6.6 to 15 years old. Only three received trientine as initial therapy [parental choice (two), allergic reactions to penicillamine (one) during the penicillamine challenge], 13 of 16 were converted from penicillamine to trientine because of reactions to penicillamine: haematuria in four, bone marrow suppression in three, neutropenia in three. Trientine was discontinued in three due to allergic rash, low copper excretion and one with compliance problems requiring transplantation. Seventy-five per cent of children presented with chronic liver disease. Kayser-Fleischer rings were noticed in eight of 16, Wilson Ferenci score range was between 4 and 10 (nl < 4). Laboratory indices remained relatively stable. In line with previous reports, trientine was used mainly as secondary treatment when there were severe side effects with penicillamine. Whilst the current evidence is low quality, it appears that trientine is as efficacious as penicillamine and small population studies show a lower side effect profile.

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“…Clinical experience with TETA (in the form of trientine) has been predominantly limited to patients with Wilson's disease (1,16,(54)(55)(56)(57)(58)(59)(60)(61)(62)(63)(64)(65)(66)(67). The reported side effects are summarized in Table 3.…”

Section: Adverse Drug Reactions Toxicity and Safetymentioning

confidence: 99%

Triethylenetetramine Pharmacology and Its Clinical Applications

2010

Molecular Cancer Therapeutics

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Triethylenetetramine (TETA), a Cu II -selective chelator, is commonly used for the treatment of Wilson's disease. Recently, it has been shown that TETA can be used in the treatment of cancer because it possesses telomerase inhibiting and anti-angiogenesis properties. Although TETA has been used in the treatment of Wilson's disease for decades, a comprehensive review on TETA pharmacology does not exist. TETA is poorly absorbed with a bioavailability of 8 to 30%. It is widely distributed in tissues with relatively high concentrations measured in liver, heart, and kidney. It is mainly metabolized via acetylation, and two major acetylated metabolites exist in human serum and urine. It is mainly excreted in urine as the unchanged parent drug and two acetylated metabolites. It has a relatively short half-life (2 to 4 hours) in humans. The most recent discoveries in TETA pharmacology show that the major pharmacokinetic parameters are not associated with the acetylation phenotype of N-acetyltransferase 2, the traditionally regarded drug acetylation enzyme, and the TETA-metabolizing enzyme is actually spermidine/spermine acetyltransferase. This review also covers the current preclinical and clinical application of TETA. A much needed overview and up-to-date information on TETA pharmacology is provided for clinicians or cancer researchers who intend to embark on cancer clinical trials using TETA or its close structural analogs. Mol Cancer Ther; 9(9); 2458-67. ©2010 AACR.

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Wilson's Disease Treatment by Triethylene Tetramine Dihydrochloride (Trientine, 2HCI): Long-Term Observations

Cited by 18 publications

References 5 publications

A copper(II)-selective chelator ameliorates left-ventricular hypertrophy in type 2 diabetic patients: a randomised placebo-controlled study

A copper(II)-selective chelator ameliorates left-ventricular hypertrophy in type 2 diabetic patients: a randomised placebo-controlled study

Triethylene tetramine dihydrochloride (trientine) in children with Wilson disease: experience at King’s College Hospital and review of the literature

Triethylenetetramine Pharmacology and Its Clinical Applications

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