ピリメタミンおよびスルファジアジン
**ピリメタミンおよびスルファジアジン**は、相乗効果を持つ抗菌・抗原虫薬の配合剤であり、獣医療では主に *Sarcocystis neurona* を原因とする**馬原虫性脊髄脳炎 (EPM)** の治療に使用されます。 * **相乗作用:** スルファ剤とジアミノピリミジン系薬を組み合わせることで、葉酸合成経路を連続的に阻害し、感受性のある原虫や細菌を死滅させます。 * **適応外使用:** FDAでは馬用としてのみ承認されていますが、小動物医療において、猫の**トキソプラズマ症**や犬の**ネオスポラ症**などの重篤な原虫感染症の治療に適応外で使用されることがあります。 * **臨床上の注意:** EPMの治療には長期（通常3〜9ヶ月）の投薬が必要です。全身性の葉酸欠乏による骨髄抑制のリスクがあるため、獣医師による慎重なモニタリングが不可欠です。
作用機序: This combination exerts its antiprotozoal and antibacterial effects through a **sequential blockade** of the folic acid synthesis pathway, which is essential for nucleic acid (DNA/RNA) production in the parasite: 1. **Sulfadiazine** acts as a structural analogue of para-aminobenzoic acid (**PABA**). It competitively inhibits the enzyme **dihydropteroate synthase**, blocking the conversion of PABA → **dihydrofolic acid (DFA)**. 2. **Pyrimethamine** specifically targets and inhibits the enzyme **dihydrofolate reductase**, blocking the conversion of DFA → **tetrahydrofolic acid (THFA)** (the active form of folate). > **Pharmacological Pearl:** Pyrimethamine has a much higher affinity for protozoal dihydrofolate reductase compared to bacterial or mammalian forms, making it highly effective against protozoal parasites like *Sarcocystis neurona* and *Toxoplasma gondii*.
動物種別の用量
- Treatment of EPM · 20 mg/kg sulfadiazine with 1 mg/kg pyrimethamine; equivalent to 4 mL of ReBalance suspension per 50 kg (110 lb) body weight · PO · once daily · 90-270 days (based upon clinical response) · Administer at least 1 hour before feeding with hay or grain. Administer using a suitable oral dosing syringe; insert nozzle through the interdental space and deposit the dose on the back of the tongue.
- Maintaining clinical remission (for horses that have had two relapses) · pyrimethamine/sulfadiazine · PO · twice weekly (first and fourth day of each week) · Ongoing · After completing regular therapy for EPM.
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
- Hypersensitivity to pyrimethamine or sulfadiazine
- Horses intended for human consumption
有害事象
- Bone marrow suppression (anemia, leukopenia, neutropenia, thrombocytopenia)
- Reduced appetite or anorexia
- Loose stools or diarrhea
- Urticaria (hives)
- Treatment crisis (temporary worsening of neurologic signs due to parasite die-off)
- CNS effects (seizures, depression - though often secondary to the underlying EPM)
薬物相互作用
- Antacids · May decrease the bioavailability of sulfonamides if administered concurrently.
- Highly protein-bound drugs (e.g., methotrexate, phenylbutazone, thiazide diuretics, salicylates, probenecid, phenytoin, warfarin) · Sulfonamides may displace other highly bound drugs, potentially increasing their free (active) plasma concentrations and risk of toxicity.
- p-Aminobenzoic acid (PABA) · Reportedly antagonistic towards the activity of pyrimethamine; clinical significance is unclear.
- Trimethoprim · Use with pyrimethamine/sulfa is not recommended in humans as adverse effects may be additive; however, this combination has been used clinically in horses.
モニタリング
- CBC (including platelets): baseline and at least monthly during therapy
- GI adverse effects (appetite, stool consistency)
- Clinical Efficacy: Improvement in neurologic signs
- CSF Western Blot test (monitoring for negative status)
過量投与
Acute overdosage information (>2X) in horses is not well documented. When administered at **2X the labeled dose for 92 days**, signs included loose stools, slight increases in ALP, declines in red blood cell parameters (RBC, HCT, Hgb, PCV), and depressed appetite. Treatment should 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。