Triethylenetetramine

Triethylenetetramine Uses, Dosage, Side Effects, Food Interaction and all others data.

Triethylenetatramine (TETA) is a highly selective divalent Cu(II) chelator and orphan drug that revereses copper overload in tissues. Its salt form, trientine (triethylenetetramine dihydrochloride or 2,2,2-tetramine) was introduced in 1969 as an alternative to D-penicillamine. It consists of a polyamine-like structure different from D-penicillamine, as it lack sulfhydryl groups. It was previously approved by FDA in 1985 as second-line pharmacotherapy for Wilson's disease. Although penicillamine treatment is believed to be more extensive, TETA therapy has been shown to be an effective initial therapy, even with patients with decompensated liver disease at the outset, and prolonged TETA treatment is not associated with adverse effects as expected in penicillamine treatment. Its clinical applications on cancer, diabetes mellitus, Alzheimer's disease and vascular demetia are being studied.

TETA is a selective copper (II) chelator. tightly binds and facilitates systemic elimination of Cu(II) into the urine whilst neutralizing its catalytic activity, but does not cause systemic copper deficiency even after prolonged use. It may also act as an antioxidant as it suppresses the copper-mediated oxidative stress. TETA not only increases urinary Cu excretion, but also decreases intestinal copper absorption by 80%.

Triethylenetetramine
Uses
Dosage
Side Effect
Precautions
Interactions
Uses during Pregnancy
Uses during Breastfeeding
Accute Overdose
Food Interaction
Half Life
Volume of Distribution
Clearance
Interaction With other Medicine
Contradiction
Storage

Trade Name	Triethylenetetramine
Generic	Triethylenetetramine
Triethylenetetramine Other Names	TETA, Trien, Trientine
Type
Formula	C₆H₁₈N₄
Weight	Average: 146.2339 Monoisotopic: 146.153146596
Groups	Approved, Investigational
Therapeutic Class
Manufacturer
Available Country
Last Updated:	September 19, 2023 at 7:00 am

Uses

Triethylenetetramine is a copper chelating agent used for the management of Wilson's disease in cases where penicillamine therapy is clinically inappropriate.

Trientine is a copper chelator used in the treatment of Wilson's disease as an alternative to D-penicillamine. It tends to be used in patients who are experiencing serious adverse effects from penicillamine therapy or intolerance of penicillamine.

Triethylenetetramine is also used to associated treatment for these conditions: Wilson's Disease

How Triethylenetetramine works

Copper is chelated by forming a stable complex with the four constituent nitrogens in a planar ring as copper displays enhanced ligand binding properties for nitrogen compared to oxygen. It binds Cu(II) very tightly, having a dissociation constant from Cu(II) of 10^−15 mol/L at pH 7.0 . TETA reacts in a stoichiometric ratio 1:1 with copper and is also able to complex with iron and zinc in vivo. TETA is considered a potential chemotherapeutic agent as it could be a telomerase inhibitor because it is a ligand for G-quadruplex, and stabilizes both intra- and intermolecular G-quadruplexes. It may mediate a selective inhibitory effect or cytotoxicity on tumor growth. Chelating excess copper may affect copper-induced angiogenesis. Other mechanisms of action of TETA for alternative therapeutic implications include improved antioxidant defense against oxidative stress, pro-apoptosis, and reduced inflammation.

Toxicity

Neurological worsening may be associated with TETA therapy. Trientine also chelates iron, and co-administration of trientine and iron should be avoided because the complex with iron is toxic. A reversible sideroblastic anemia may be a consequence of overtreatment and resultant copper deficiency. Lupus-like reactions have also been reported . The oral LD50 value in rats is rat, mouse, rabbit is 2500mg/kg, 1600mg/kg, and 5500mg/kg, respectively.

Food Interaction

Take at least 2 hours before or after iron supplements. Iron and triethylenetetramine inhibit each others absorption.
Take on an empty stomach. Take triethylenetetramine one hour before or two hours after eating a meal or at least one hour of separation from other drugs, milk, or food.

Volume of Distribution

It is widely distributed in tissues with relatively high concentrations measured in liver, heart, and kidney. A recent study reported that the central and peripheral volumes of distribution were 393 L and 252 L, respectively .

Elimination Route

It is poorly absorbed from the gastrointestinal tract with a bioavailability of 8 to 30% and and what is absorbed is metabolized and inactivated. 5% to 18% that is systemically absorbed in humans is reported to be extensively metabolized . The time to reach peak concentration (Tmax) for humans occur between 0.8 to 4 hours .

Half Life

The plasma elimination half life of TETA in healthy volunteers and Wilson's disease patients ranges from 1.3 to 4 hours. The metabolites are expected to be longer than the parent drug.

Elimination Route

The unchanged drug and two acetylated metabolites, N1-acetyltriethylenetetramine (MAT) and N1,N10-diacetyltriethylenetetramine (DAT), are mainly excreted in the urine. About 1% of the administered trientine and about 8% of the biotransformed trientine metabolite, acetyltrien, ultimately appear in the urine. The amounts of urinary copper, zinc and iron increase in parallel with the amount of trientine excreted in the urine . Unchanged drug is also excreted in feces after oral administration.