What are the possible metabolic fates of diethyldithiocarbamate (DDTC)?

Disulfiram is rapidly biotransformed into metabolic products, and further metabolism occurs via DDTC.

Once disulfiram is reduced, all further metabolism takes place via diethyldithiocarbamate (DDTC), which has three possible metabolic fates:

Spontaneous degradation: DDTC is acid-labile and its half-life is a linear function of its pH. In an acidic environment, such as the stomach, DDTC decomposes to diethylamine and carbon disulfide (CS2 ). CS2 can be detected in the blood and breath of humans after disulfiram administration; after a 250 mg oral dose, the half-life of CS2 is roughly 12 hours and can be detected in breath up to 72 hours later.

Formation of glucuronide: The enzyme glucuronosyltransferase, highly expressed in the liver, forms glucuronide from DDTC. This glucuronide accounts for 2-11% of the administered disulfiram dose that is excreted in the urine.

Formation of methyl esters: The enzymes thiol methyltransferase (microsomal) and possibly thiopurine methyltransferase (cytosolic), found in the liver and other tissues, catalyze the methylation of DDTC. This leads to the formation of the lipophilic metabolite DDTC-Me (methyl diethyldithiocarbamate), which is further oxidized to DETC-Me (methyl diethylthiocarbamate), and then biotransformed into additional metabolites that aid in the irreversible inhibition of the ALDH enzyme.