チオプロニン (Tiopronin)
**チオプロニン**は、主に犬の**シスチン尿路結石**（膀胱結石）の管理と予防に使用される専門的な**抗尿路結石薬**です。シスチン尿症は、特定のアルギニン酸（特にシスチン）の尿細管再吸収における遺伝性代謝異常であり、シスチンは酸性尿中で非常に溶けにくく、結石を形成しやすくなります。 食事療法（超低タンパク質、アルカリ化食）や尿のアルカリ化だけでは結石の溶解や再発予防が不十分な場合に、チオプロニンが通常使用されます。 * **主な特徴：** * 尿中のシスチン溶解度を高める**キレート剤**として作用します。 * ペニシラミンと比較して副作用の発生率が低い可能性があるため好まれることが多いですが、比較的高価です。 * 予防を成功させるには、生涯にわたる治療と飼い主の厳格なコンプライアンスが必要です。
作用機序: 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**.
動物種別の用量
- 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
用量は獣医療従事者向けの臨床リファレンスです。必ず最新の添付文書と個々の患者で確認してください。
投与経路
禁忌
- Agranulocytosis
- Aplastic anemia
- Thrombocytopenia or other significant hematologic abnormality
- Impaired renal or hepatic function
- Sensitivity to either tiopronin or penicillamine
有害事象
- 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
薬物相互作用
- Nephrotoxic drugs · Potentially additive toxic effects
- Hepatotoxic drugs · Potentially additive toxic effects
- Bone marrow depressing drugs · Potentially additive toxic effects
モニタリング
- 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)
過量投与
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 の薬剤リファレンスは、獣医療従事者向けの臨床意思決定支援を目的としており、専門的判断やメーカーの最新添付文書に代わるものではありません。