Tiopronin Explained

Tradename:	Thiola
Dailymedid:	Tiopronin
Drugbank:	DB06823
Chebi:	32229

Tiopronin, sold under the brand name Thiola, is a medication used to control the rate of cystine precipitation and excretion in the disease cystinuria.^{[1] [2]}

It is available as a generic medication.^{[3] [4]}

Medical uses

Tiopronin is indicated, in combination with high fluid intake, alkali, and diet modification, for the prevention of cystine stone formation in people 20kg (40lb) and greater with severe homozygous cystinuria, who are not responsive to these measures alone.

Side effects

Tiopronin may present a variety of side effects, which are broadly similar to those of D-penicillamine and other compounds containing active sulfhydryl groups.^[5] Its pharmacokinetics have been studied.

Pharmacology

Mechanism of action

Tiopronin works by reacting with urinary cysteine to form a more soluble, disulfide linked, tiopronin-cysteine complex.^[6]

Society and culture

In the U.S., the drug was marketed by Mission Pharmacal at $1.50 per pill, but in 2014 the rights were bought by Retrophin, owned by Martin Shkreli, and the price increased to $30 per pill for a 100 mg capsule.^{[7] [8]}

In 2016 Imprimis Pharmaceuticals introduced a lower cost version marketed as a compounded drug.^[9]

Research

It may also be used for Wilson's disease (an overload of copper in the body), and has also been investigated for the treatment of arthritis,^{[10] [11]} though tiopronin is not an anti-inflammatory.

Tiopronin is also sometimes used as a stabilizing agent for metal nanoparticles. The thiol group binds to the nanoparticles, preventing coagulation.^[12]

Notes and References

1. Lindell A, Denneberg T, Hellgren E, Jeppsson JO, Tiselius HG . Clinical course and cystine stone formation during tiopronin treatment . Urological Research . 23 . 2 . 111–7 . 1995 . 7676533 . 10.1007/BF00307941 . 34308815 .
2. Coe FL, Parks JH, Asplin JR . The pathogenesis and treatment of kidney stones . The New England Journal of Medicine . 327 . 16 . 1141–52 . October 1992 . 1528210 . 10.1056/NEJM199210153271607 .
3. Web site: Competitive Generic Therapy Approvals . U.S. Food and Drug Administration (FDA) . 29 June 2023 . 29 June 2023 . 29 June 2023 . https://web.archive.org/web/20230629233651/https://www.fda.gov/drugs/generic-drugs/competitive-generic-therapy-approvals . live .
4. Web site: First Generic Drug Approvals 2023 . U.S. Food and Drug Administration (FDA) . 30 May 2023 . https://web.archive.org/web/20230630003621/https://www.fda.gov/drugs/drug-and-biologic-approval-and-ind-activity-reports/first-generic-drug-approvals . 30 June 2023 . live . 30 June 2023.
5. Jaffe IA . Adverse effects profile of sulfhydryl compounds in man . The American Journal of Medicine . 80 . 3 . 471–6 . March 1986 . 2937293 . 10.1016/0002-9343(86)90722-9 .
6. Carlsson MS, Denneberg T, Emanuelsson BM, Kågedal B, Lindgren S . Pharmacokinetics of oral tiopronin . European Journal of Clinical Pharmacology . 45 . 1 . 79–84 . August 1993 . 8405034 . 10.1007/BF00315354 . 8879752 .
7. News: Lowe D . The Most Unconscionable Drug Price Hike I Have Yet Seen. In the Pipeline. 11 September 2014.
8. Web site: Why would Martin Shkreli hike an old drug price by 5000%? Only a 'moron' would ask. FierceBiotech . Carroll J . September 20, 2015.
9. News: Elvidge S . Imprimis shuts down Texas plant, axes 8% of jobs. BioPharma Dive. September 29, 2016.
10. Delecoeuillerie G . [Tolerability and therapeutic maintenance of tiopronin, new basic treatment of rheumatoid arthritis. Apropos of long-term follow-up of 268 cases] . Revue du Rhumatisme et des Maladies Osteo-Articulaires . 56 . 5 Pt 2 . 38–42 . April 1989 . 2740804 .
11. Pasero G, Pellegrini P, Ambanelli U, Ciompi ML, Colamussi V, Ferraccioli G, Barbieri P, Mazzoni MR, Menegale G, Trippi D . 6 . Controlled multicenter trial of tiopronin and d-penicillamine for rheumatoid arthritis . Arthritis and Rheumatism . 25 . 8 . 923–9 . August 1982 . 7115451 . 10.1002/art.1780250803 .
12. Dahl JA, Maddux BL, Hutchison JE . Toward greener nanosynthesis . Chemical Reviews . 107 . 6 . 2228–69 . June 2007 . 17564480 . 10.1021/cr050943k . amp . 10.1.1.454.2724 .