ピリメタミン
ピリメタミンは強力な**抗原虫薬**であり、獣医学では主に小動物の**トキソプラズマ症**、**ネオスポラ症**、***Hepatozoon americanum*** などの重篤な原虫感染症や、馬の**馬原虫性脊髄脳炎（EPM）**の治療に使用されます。葉酸合成を相乗的に阻害するため、ほぼ常にサルファ剤と併用されます。 **臨床のポイント：** 葉酸代謝を標的とするため、特に猫において宿主の骨髄抑制が重大なリスクとなります。血液毒性を軽減するために、ホリナート（葉酸ではなく、原虫が利用できない形態）やパン酵母の補給がしばしば推奨されます。
作用機序: Pyrimethamine is a **folic acid antagonist**. It competitively inhibits the enzyme **dihydrofolate reductase (DHFR)** → blocks the reduction of **dihydrofolic acid** to **tetrahydrofolic acid** (the active form of folate) → depletes folate reserves essential for purine and pyrimidine synthesis → halts protozoal DNA and RNA synthesis. When combined with sulfonamides (which inhibit **dihydropteroate synthase** earlier in the pathway), it produces a synergistic, sequential blockade of the folate synthesis pathway.
動物種別の用量
- Toxoplasmosis · 0.5-1 mg/kg PO once daily for 2 days, then 0.25 mg/kg PO once daily for 2 weeks · PO · once daily · 2 days, then 2 weeks · Given with sulfadiazine at 30-50 mg/kg PO divided two to four times a day for 1-2 weeks
- Toxoplasmosis (enteroepithelial cycle) · 2 mg/kg, PO once daily · PO · once daily
- Toxoplasmosis (extraintestinal cycle) · 0.5-1 mg/kg PO divided two to three times daily · PO · divided two to three times daily · Combined with sulfonamides (e.g., triple sulfa, sulfadiazine) at 60 mg/kg PO or IM divided two to three times daily
- Protozoal myocarditis · 1 mg/kg PO once daily for 3 days, then decrease dose to 0.5 mg/kg PO once a day · PO · once daily · 3 days, then ongoing · Given with sulfadimethoxine 25 mg/kg PO, IV, or IM once a day
- Toxoplasmosis · 0.5 mg/kg PO per day · PO · per day · 7-10 days · Given with sulfadiazine at 30 mg/kg, PO q12h. Do not use continuously for longer than 2 weeks. Supplementation with folic acid 5 mg/day or folinic acid 1 mg/kg/day may alleviate toxicity.
- Equine protozoal myeloencephalitis · 1 mg/kg PO once a day for 90-120 days (or longer) · PO · once a day · 90-120 days (or longer) · Given with a sulfa or potentiated sulfa (sulfadiazine 20 mg/kg PO once or twice a day). Monitor CBC's.
- Coccidian organisms in raptors (Toxoplasmosis, Atoxoplasmosis, Sarcocystis) · 0.5 mg/kg PO twice daily for 14-28 days · PO · twice daily · 14-28 days
- Toxoplasmosis · 0.5-1 mg/kg PO once daily for 2 days, then 0.25 mg/kg PO once daily for 2 weeks · PO · once daily · 2 days, then 2 weeks · Given with sulfadiazine at 30-50 mg/kg PO divided two to four times a day for 1-2 weeks
- Toxoplasmosis · 0.25-0.5 mg/kg once daily for 28 days · PO · once daily · 28 days
- Neospora · 1 mg/kg once daily for 28 days · PO · once daily · 28 days · Given with trimethoprim sulfa
- Hepatazoon canis · 0.25-0.5 mg/kg once daily for 2-4 weeks · PO · once daily · 2-4 weeks · Given with trimethoprim sulfa and clindamycin
- Hepatazoon americanum · 0.25 mg/kg PO q24h · PO · q24h · Given with Trimethoprim/sulfa (15 mg/kg PO q12h) and clindamycin (10 mg/kg q8h). Once remission attained, decoquinate can maintain.
- Hepatazoon americanum · 0.25 mg/kg PO q24h for 14 days · PO · q24h · 14 days · Given with Trimethoprim/sulfa (15 mg/kg PO q12h for 14 days) and clindamycin (10 mg/kg q8h for 14 days). Once remission attained, decoquinate can maintain.
- Neosporosis · 1 mg/kg PO daily · PO · daily · Given with trimethoprim/sulfa (15-30 mg/kg 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
- Known hypersensitivity to pyrimethamine
- Preexisting hematologic disorders (use with extreme caution)
- Pregnancy (potentially teratogenic, weigh risks vs. benefits)
- Pregnancy (teratogenic)
- Pre-existing bone marrow suppression
- Hypersensitivity to pyrimethamine
有害事象
- Small animals: Anorexia, malaise, vomiting, depression
- Small animals: Bone marrow depression (anemia, thrombocytopenia, leukopenia)
- Cats: Highly susceptible to adverse reactions (noted 4-6 days after starting combination therapy)
- Horses: Leukopenias, thrombocytopenia, and anemias
- Bone marrow suppression (anemia, leukopenia, thrombocytopenia)
- Anorexia
- Vomiting
- Lethargy
- Depression
薬物相互作用
- p-Aminobenzoic acid (PABA) · Reportedly antagonistic towards the activity of pyrimethamine; clinical significance is unclear.
- Sulfonamides · Synergistic with pyrimethamine in activity against toxoplasmosis and malaria. · moderate
- 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. · major
- Phenobarbital · May increase folate deficiency · moderate
- Phenytoin · May increase folate deficiency · moderate
モニタリング
- CBC with platelet count (frequent monitoring recommended)
- Clinical efficacy
- Signs of abnormal bleeding or lassitude
- Complete Blood Count (CBC) every 1-2 weeks
- Appetite and body weight
- Signs of bleeding, bruising, or lethargy
過量投与
Reports of acute overdosage in animals were not located. In humans, signs include **vomiting, nausea, anorexia, CNS stimulation (including seizures), and hematologic effects**. **Treatment recommendations:** - Standard procedures to empty the gut or prevent absorption. - Parenteral barbiturates for seizures. - Folinic acid for hematologic effects. - Long-term monitoring (at least 1 month) of renal and hematopoietic systems.
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。