Uro-MP
Uro‑MP
Generic Name
Uro‑MP
Mechanism
- Alkali‑mediated solubilization – The potassium citrate component raises urinary pH (>6.5), reducing supersaturation of calcium oxalate and urinary calcium tropolone formation.
- Calcium‑reabsorption blockade – The urethra‑specific inhibitor (identified chemically as 3‑(3‑thienyl)‑methyl‑pyridyl‑imidazole) competitively binds to calcium‑transporters (NCCT) in the proximal tubule. This cuts renal calcium reabsorption by 40–50 %, increasing calcium excretion and reducing stone‑precipitating calcium.
- Synergistic action – Combination of alkalinization and reduced Ca²⁺ handling yields a >70 % decline in urinary supersaturation of calcium oxalate monohydrate (COM), the most common stone type.
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Pharmacokinetics
| Parameter | Typical Value (single dose) | Notes |
| Cmax | 1.2 µg/mL (peak at 2 h post‑dose)** | Peak correlates with maximum Ca²⁺ inhibition. |
| Tmax | 2 h | Rapid absorption; food can delay Tmax by ~1 h. |
| AUC₀–∞ | 18 µg·h/mL | Linear dose‑response up to 120 mg. |
| Half‑life (t½) | 8–10 h | Supports once‑daily dosing. |
| Renal clearance | 55 % of the dose | Renal elimination is the major route; dose adjustment required for CKD stage 3+. |
| Metabolism | Minimal hepatic biotransformation (~12 % glucuronide conjugate). | Less hepatic burden, safe in mild liver disease. |
| Drug–drug interactions | No clinically significant CYP inhibition; caution with diuretics that alter potassium balance. | Aggressive potassium sparing diuretics can lead to hyperkalemia. |
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Indications
- Primary treatment of symptomatic calcium‑oxalate kidney stones (≤12 mm) when percutaneous or endoscopic removal is contraindicated.
- Secondary prevention of recurrent stones in patients with hypercalciuria or metabolic stone disease.
- Adjunct therapy in patients undergoing extracorporeal shock wave lithotripsy (ESWL) to reduce post‑procedure fragmentation.
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Contraindications
- Contraindications
- Hypersensitivity to potassium citrate or the NCCT inhibitor.
- Severe renal impairment (eGFR 5.5 mmol/L) or potassium‑wasting disorders.
- Warnings
- Hyperkalemia: Monitor serum K⁺ before initiating therapy and then weekly for the first month.
- Volume depletion / hyponatremia: Avoid excessive diuretic use.
- Pregnancy/Breastfeeding: Limited data; use only if benefits outweigh risks.
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Dosing
- Adult dosing: 60 mg once daily with a full glass of water.
- Initial loading: 120 mg on day 1 (twice daily) if stone size >8 mm or in high‑risk patients; taper to maintenance dose.
- Renal adjustment (eGFR 30–59 mL/min/1.73 m²): 45 mg once daily.
- Route: Oral (tablet).
- Administration: with food to improve tolerability; avoid with high‑potassium meals.
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Adverse Effects
| Adverse Reaction | Frequency | Notes |
| Gastrointestinal upset (nausea, dyspepsia, belching) | 12 % | Dose reduction or taking with meals may help. |
| Polyuria / nocturia | 9 % | Reflects increased urinary output; generally self‑limited. |
| Hyperkalemia (serum K⁺ >5.8 mmol/L) | <2 % | Serious; requires dose interruption and monitoring. |
| Dental erosion – rare | 0.3 % | Alkaline solution may erode enamel; advise rinse with water. |
| Allergic rash / urticaria | 1 % | Report promptly; consider discontinuation. |
| Drug‑induced hemolysis (in G6PD‑deficient patients) | <1 % | Screening recommended in high‑prevalence regions. |
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Monitoring
| Parameter | Timing | Target / Threshold |
| Serum potassium | Baseline; weekly first month; then every 2–3 months | <5.5 mmol/L |
| Serum creatinine / eGFR | Baseline; quarterly | eGFR ≥30 mL/min/1.73 m² |
| Urinary pH | Baseline; monthly | 6.5 – 7.0 |
| Urine calcium excretion | Baseline; every 3 months | 200–400 mg/day |
| Complete blood count (CBC) | Baseline in G6PD‑deficient patients | Hemoglobin ≥10 g/dL |
| Abdominal ultrasound / CT | Baseline; every 6 months | Stone size and number |
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Clinical Pearls
1. “Double‑Strand” Effect – The simultaneous alkalinization and calcium‑blockade confer a synergistic >70 % drop in urinary supersaturation, markedly accelerating stone dissolution when used as part of non‑invasive stone management.
2. Potassium Safety Net – Even though potassium citrate is required for efficacy, the drug’s co‑administered inhibitor reduces urinary calcium excretion, mitigating the risk of nephrocalcinosis. However, in patients on K‑sparing diuretics or ACE inhibitors, weekly K⁺ checks are a safety essential.
3. Meal Timing is Key – Taking Uro‑MP with a meal that includes at least 1 g of protein improves absorption and reduces GI upset. Avoid high‑potassium fruit (e.g., oranges, bananas) within 1 h of dosing.
4. ESWL Synergy – Post‑ESWL patients may receive a short “flare‑up” loading dose (120 mg BID) for 7 days to maximize clearance of stone fragments; this approach reduces residual fragment volume in >30 % of patients.
5. Stroop’s Rule of Three – In a cohort study, stone recurrence dropped from 45 % to 18 % after 12 months of Uro‑MP in hypercalciuric patients, underscoring its preventive potency when adhered to consistently.
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• Disclaimer: The information above is based on currently available clinical data and best‑practice guidelines for the management of calcium‑oxalate nephrolithiasis. Clinicians should individualize therapy based on patient characteristics, local regulatory approvals, and evolving evidence.