Indications
Tiopronin is primarily indicated for the prevention of kidney stone formation in patients diagnosed with severe homozygous cystinuria. This condition is characterized by a urinary cystine concentration exceeding 500 mg per day. Tiopronin is recommended for individuals who have not responded adequately to non-pharmacological interventions such as increased fluid intake, reduced sodium and protein consumption, and urine alkalinization.
Absorption
Tiopronin exhibits a slow absorption profile, with peak plasma concentrations occurring approximately 3 to 6 hours post-ingestion. In studies conducted on healthy individuals, the bioavailability of Tiopronin was determined to be 63% for the total compound and 40% for the unbound form. These findings suggest moderate absorption rates that should be considered when determining dosing regimens.
Metabolism
Tiopronin is metabolized primarily into 2-mercaptopropionic acid (2-MPA) through the process of hydrolysis. It is estimated that between 10% to 15% of the administered dose is converted to this principal metabolite. This metabolic pathway plays a crucial role in the drug's overall pharmacokinetic profile and efficacy.
Mechanism of Action
KiDespite cystine's low solubility in urine, leading to kidney stone formation when its concentration exceeds the solubility limit, tiopronin offers a viable solution by introducing an effective mechanism to prevent this. Tiopronin acts as a potent reducing agent, engaging in a thiol-disulfide exchange reaction with cystine. This interaction transforms cystine into a water-soluble mixed disulfide complex, significantly decreasing the amount of cystine available to form poorly soluble deposits. By effectively lowering urinary cystine concentrations to levels below its solubility threshold, tiopronin plays a crucial role in mitigating the development of cystine stones.
