Tiopronin
**Tiopronin** is a specialized **antiurolithic agent** primarily used in veterinary medicine to manage and prevent **cystine urolithiasis** (bladder stones) in dogs. Cystinuria is an inherited metabolic defect in the renal tubular reabsorption of certain amino acids, notably cystine, which is highly insoluble in acidic urine and prone to forming calculi. Tiopronin is typically employed when dietary modifications (ultra-low protein, alkalinizing diets) and urinary alkalinization fail to dissolve or prevent the recurrence of these stones. * **Key Features:** * Acts as a **chelating agent** to increase cystine solubility in the urine. * Often preferred over penicillamine due to a potentially lower incidence of adverse effects, though it remains relatively expensive. * Requires lifelong therapy and strict owner compliance for prophylactic success.
Mechanism: Tiopronin is an active **sulfhydryl (-SH) compound**. In the urine, it undergoes a **thiol-disulfide exchange** with cystine (which is a cysteine-cysteine disulfide). * **Mechanism Pathway:** Tiopronin + Cystine → **Tiopronin-Cysteine Disulfide Complex** + Cysteine. * This newly formed complex is up to 50 times more water-soluble than cystine alone. * By increasing the solubility of cystine in the urine, tiopronin prevents the precipitation of cystine crystals and facilitates the gradual dissolution of existing **cystine calculi**.
Dosing by species
- Prophylactic treatment of cystine urinary calculi · 30 mg/kg PO q12h · PO · q12h · Increase water intake and urine diuresis. Alkalinize urine (pH 6.5-7.0) using potassium citrate. In cases with low cystine excretion and low urolith recurrence rate, tiopronin dose may be individually decreased (<30 mg/kg) or stopped.
- Dissolution of uroliths · Approximately 40 mg/kg PO q12h · PO · q12h · Reevaluation of uroliths with ultrasound or radiography every 4th week. After urolith dissolution, give prophylactic dose. If urolith dissolution is not achieved after 2-3 months, surgery is recommended.
- In conjunction with an alkalinizing, protein and sodium restricted diet (e.g., u/d) · 30-40 mg/kg PO divided into two daily doses · PO · divided into two daily doses
- Treatment of cystine urinary calculi · 20 mg/kg PO twice daily · PO · twice daily · 1-3 months · Relatively high incidence of adverse effects
- Prevention of cystine urinary calculi · 15 mg/kg PO twice daily · PO · twice daily
Doses are a clinical reference for licensed veterinary professionals. Always confirm against the current label and the individual patient.
Routes of administration
Contraindications
- Agranulocytosis
- Aplastic anemia
- Thrombocytopenia or other significant hematologic abnormality
- Impaired renal or hepatic function
- Sensitivity to either tiopronin or penicillamine
Adverse effects
- Coombs'-positive regenerative spherocyte anemia
- Aggressiveness
- Proteinuria
- Thrombocytopenia
- Elevations in liver enzymes and bile acids
- Dermatologic effects (small pustules, dry crusty nose, ecchymosis, itching, rashes, mouth ulcers, jaundice)
- Myopathy (staggering, difficulty chewing)
- Lethargy
- Sulfur odor of the urine
- GI distress
- Allergic reactions (adenopathy)
- Arthralgias
- Dyspnea
- Fever
- Edema
- Nephrotic syndrome
Drug interactions
- Nephrotoxic drugs · Potentially additive toxic effects
- Hepatotoxic drugs · Potentially additive toxic effects
- Bone marrow depressing drugs · Potentially additive toxic effects
Monitoring
- Physical examination (1, 3, 6, & 12 months after start, then twice a year)
- Ultrasonography/radiography of the urinary tract
- Urinalyses (specific gravity, protein, pH, sediment, and cyanide nitroprusside reaction) using AM samples
- CBC (with platelets)
- Liver enzymes (alkaline phosphatase, ALT)
- Quantitative measurements of urinary cystine excretion related to urinary creatinine excretion (AM samples, before start and once a year during treatment)
Overdose
There is little information available regarding acute toxicity or overdosage of tiopronin in veterinary species. It is suggested to contact an animal poison control center for further information and guidance in the event of an overdose situation. Treatment would likely be supportive and symptomatic.
VetSheet drug reference is intended for licensed veterinary professionals as a clinical decision-support aid, not a substitute for professional judgement or the manufacturer’s current label.