アロプリノール
**アロプリノール**は、獣医学で広く使用されている強力な**キサンチンオキシダーゼ阻害薬**です。 主な臨床応用は以下の通りです： * **尿酸塩尿石症：** 主に犬（特にダルメシアンなどの好発犬種）の尿酸結石の溶解および予防に使用されます。キサンチン結石の形成を防ぐため、低プリン食と併用する必要があります。 * **犬リーシュマニア症：** リーシュマニア静菌薬として作用します。長期管理のためにメグルミンアンチモネートやミルテホシンと併用されることがよくあります。 * **鳥類および爬虫類医学：** 鳥類や爬虫類の高尿酸血症の管理および痛風の治療に使用されます。 *臨床のポイント：* アロプリノールはキサンチンの尿中排泄を増加させるため、食事でのプリン制限を行わずに長期高用量投与すると、逆説的にキサンチン尿石の形成を招く可能性があります。
作用機序: Allopurinol and its primary active metabolite, **oxypurinol** (alloxanthine), competitively inhibit the enzyme **xanthine oxidase**. * **Normal Pathway:** Hypoxanthine → **xanthine oxidase** → Xanthine → **xanthine oxidase** → Uric Acid * **Inhibition:** By blocking this enzyme, allopurinol prevents the conversion of oxypurines to uric acid. This decreases serum and urine concentrations of uric acid, while increasing the levels of the more water-soluble precursors (hypoxanthine and xanthine). **In Leishmaniasis:** Allopurinol acts as a purine analogue. *Leishmania* organisms mistakenly incorporate allopurinol metabolites into their RNA, which disrupts protein synthesis and inhibits parasite multiplication.
動物種別の用量
- Urate uroliths (dissolution) · 15 mg/kg PO q12h; only in conjunction with low purine foods. · PO · q12h
- Urate uroliths (prevention) · 10-20 mg/kg/day · PO · Daily · Preferable to minimize recurrence with dietary therapy to avoid xanthine uroliths.
- Urate uroliths (dissolution and prevention) · 7-10 mg/kg PO three times daily · PO · TID · Goal is to reduce urine urate:creatinine ratio by 50%.
- Leishmaniasis (First line treatment) · 10 mg/kg PO twice daily · PO · BID · 6-12 months · Used plus Meglumine antimoniate 75-100 mg/kg once daily for 4-8 weeks.
- Leishmaniasis (Second line treatment) · 10 mg/kg PO twice daily · PO · BID · 6-12 months · Used plus Miltofosine 2 mg/kg PO once daily for 4 weeks OR allopurinol alone.
- Leishmaniasis · 20 mg/kg PO q12h · PO · q12h · 9 months · With Meglumine antimoniate (100 mg/kg/day SQ) until resolution.
- Leishmaniasis (Alternate protocol alone) · 10 mg/kg PO q8h or 10-20 mg/kg PO q12h · PO · q8h or q12h · 1-4 months
- Leishmaniasis · 10 mg/kg PO twice daily · PO · BID · If possible use with meglumine antimoniate, if not, use alone.
- Leishmaniasis (with renal insufficiency) · 5 mg/kg PO twice daily · PO · BID
- Leishmaniasis · 15 mg/kg PO twice daily · PO · BID · months
投与経路
禁忌
- Known hypersensitivity to allopurinol
- Red-tailed hawks (anecdotal reports of severe toxicity)
有害事象
- Xanthine urolithiasis (especially with high doses or non-restricted diets)
- Hypersensitivity reactions (rash, erythema)
- Lethargy
- Gastrointestinal upset
- Hepatotoxicity (rare)
- Bone marrow suppression (rare)
薬物相互作用
- Chlorpropamide · May increase risks for hypoglycemia and hepato-renal reactions
- Cyclophosphamide · Increased bone marrow depression may occur
- Cyclosporine · Allopurinol may increase cyclosporine levels
- Diuretics (Furosemide, Thiazides, Diazoxide) and Alcohol · Can increase uric acid levels, antagonizing allopurinol's effect
- Oral Anticoagulants (e.g., Warfarin) · Allopurinol may reduce the metabolism of warfarin thereby increasing its effect
- Trimethoprim/Sulfamethoxazole · Thrombocytopenia has occurred in a few human patients when used concurrently
- Uricosuric Agents (e.g., Probenecid, Sulfinpyrazone) · May increase the renal excretion of oxypurinol and thereby reduce xanthine oxidase inhibition; additive effects on blood uric acid may be beneficial
- Urinary Acidifiers (e.g., Methionine, Ammonium Chloride) · May reduce the solubility of uric acid in the urine and induce urolithiasis
- Azathioprine · Allopurinol inhibits the metabolism of azathioprine, leading to severe, potentially fatal myelosuppression. · major
- Mercaptopurine · Allopurinol inhibits the metabolism of mercaptopurine, significantly increasing toxicity risk. · major
- Amoxicillin / Ampicillin · Concurrent use increases the risk of cutaneous rash. · moderate
モニタリング
- Urine uric acid (for urolithiasis)
- Adverse effects (rash, lethargy)
- Periodic CBC, liver and renal function tests (e.g., BUN, Creatinine, liver enzymes); especially early in therapy
過量投与
Information on acute overdosage in veterinary species is limited. Massive overdoses may cause gastrointestinal distress (vomiting, diarrhea). Treatment should consist of supportive care and monitoring of renal function. Adequate hydration is important to promote diuresis and excretion.
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。