乙胺嘧啶與磺胺嘧啶
Pyrimethamine and Sulfadiazine
5-(4-chlorophenyl)-6-ethylpyrimidine-2,4-diamine; 4-amino-N-pyrimidin-2-ylbenzenesulfonamide
別名: ReBalance · Fansidar (related compound) · Pyrimethamine/Sulfadiazine
由 VetSheet 獸醫團隊審訂更新於 2026年4月5日本內容以實證獸醫文獻為本
劑量為合格獸醫專業人員的臨床參考。請務必對照最新仿單及個別病患確認。
各物種劑量
🌎 NA — North America🌍 EU — Europe
馬
| 適應症 | 劑量 | 途徑 | 頻次 | 療程 | 地區 |
|---|---|---|---|---|---|
| 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) | 🌎 NA |
| Maintaining clinical remission (for horses that have had two relapses) | pyrimethamine/sulfadiazine | PO | twice weekly (first and fourth day of each week) | Ongoing | 🌎 NA |
- Treatment of EPM: 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): After completing regular therapy for EPM.
劑量為合格獸醫專業人員的臨床參考。請務必對照最新仿單及個別病患確認。
概覽
乙胺嘧啶與磺胺嘧啶 (Pyrimethamine and sulfadiazine) 是一種具有協同作用的抗菌與抗原蟲複方藥物，在獸醫學中主要用於治療由 Sarcocystis neurona 引起的馬原蟲性脊髓腦炎 (EPM)。
- 協同作用： 透過結合磺胺類藥物與二氨基嘧啶類藥物，此配方能對葉酸合成途徑產生連續阻斷作用，對易感原蟲與細菌具有致命性。
- 仿單標示外使用 (Off-label Uses)： 雖然 FDA 僅核准用於馬匹，但此複方（或類似的葉酸拮抗劑組合）有時會在小動物臨床上用於治療嚴重的原蟲感染，例如貓的弓形蟲症 (Toxoplasmosis) 與狗的新孢子蟲症 (Neosporosis)。
- 臨床注意事項： 治療 EPM 需要長期的療程（通常為 3 到 9 個月）。由於可能引發全身性葉酸缺乏，臨床獸醫師必須密切監測骨髓抑制的風險。
作用機轉
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:
- 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).
- 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.
安全性與警告
禁忌症
- Hypersensitivity to pyrimethamine or sulfadiazine
- Horses intended for human consumption
不良反應
- 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)
注意事項
Use with extreme caution in horses with preexisting hematologic abnormalities or those receiving other bone marrow-suppressing drugs.
Pregnancy/Nursing: Pyrimethamine is teratogenic in rats, and fetal abnormalities have been seen in foals. Sulfas cross the placenta and are distributed into milk. Use in pregnant animals only when benefits clearly outweigh risks. Consider using milk replacer for nursing offspring.
Treatment Crisis: Neurologic signs may worsen during the first few days to 5 weeks of treatment due to an inflammatory reaction secondary to dying parasites in the CNS.
藥物交互作用
May decrease the bioavailability of sulfonamides if administered concurrently.
Sulfonamides may displace other highly bound drugs, potentially increasing their free (active) plasma concentrations and risk of toxicity.
Reportedly antagonistic towards the activity of pyrimethamine; clinical significance is unclear.
Use with pyrimethamine/sulfa is not recommended in humans as adverse effects may be additive; however, this combination has been used clinically in horses.
監測
- 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)
藥物動力學
半衰期
吸收
Pyrimethamine oral bioavailability is approximately 56% in horses. Sulfadiazine is well absorbed after oral administration.
分佈
Pyrimethamine CNS levels are approximately 25-50% of those found in plasma. Sulfadiazine enters the CSF; Volume of distribution is approximately 0.58 L/kg.
代謝
Hepatic metabolism (specific details not provided in monograph).
排除
Renal excretion.
過量
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.
可用產品
劑型
- Oral suspension
獸醫用
- Sulfadiazine (as the sodium salt) 250 mg/mL and Pyrimethamine 12.5 mg/mL Oral Suspension in quart (946.4 mL) bottles (ReBalance Antiprotozoal Oral Suspension)
人用標示
- Fansidar (Sulfadoxine & Pyrimethamine) - discontinued in the US market
各地核准狀態
暫無法規資料: 🇺🇸 US · 🇪🇺 EU · 🇬🇧 UK · 🇭🇰 HK · 🇹🇼 TW · 🇯🇵 JP · 🇰🇷 KR · 🇦🇺 AU
儲存與穩定性
Store at controlled room temperature (15-30°C / 59-86°F) and protect from freezing.
飼主須知
重要給藥指示
- 使用前請充分搖勻，以確保藥物均勻混合。
- 必須空腹給藥： 請在餵食乾草或穀物前至少 1 小時空腹給予此藥物。食物會阻礙藥物的正常吸收。
預期反應
- 治療危機 (Treatment Crisis)： 在治療的最初幾天到幾週內，馬匹的神經系統症狀可能會暫時惡化，這是很常見的現象。這通常是因為原蟲在神經系統中死亡所引發的發炎反應。請勿自行停藥，但務必通知您的獸醫師。
- 長期治療： EPM 的治療是一場馬拉松，而不是短跑。通常需要每天給藥，持續 3 到 9 個月。
何時應聯繫獸醫師
請密切觀察是否有藥物毒性的跡象（可能影響骨髓）。如果您發現以下情況，請立即聯繫獸醫師：
- 嚴重的抑鬱或精神不振
- 不明原因的出血或瘀傷（例如牙齦出血）
- 血便或嚴重的腹瀉
- 完全食慾不振
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