ドンペリドン
ドンペリドンは末梢性に作用する**ドパミン-2 (D2) 受容体拮抗薬**であり、主に消化管運動機能改善薬、制吐薬、およびプロラクチン分泌促進薬として使用されます。 主な臨床応用： - **馬**：周産期の牝馬におけるトールフェスク中毒の予防と治療、泌乳刺激（無乳症）、および馬下垂体中葉機能障害（PPID / 馬クッシング症候群）の診断薬として。 - **小動物**：特に胃排空遅延を伴う疾患に対する消化管運動機能改善薬および制吐薬としての適応外使用。 **臨床のポイント**：メトクロプラミドとは異なり、ドンペリドンは血液脳関門を容易に通過しません。これにより、錐体外路症状（振戦、痙攣など）のような中枢神経系（CNS）の副作用リスクが大幅に軽減され、中枢作用型の運動機能改善薬に敏感な患者にとって優れた代替薬となります。
作用機序: Domperidone exerts its effects through multiple pathways: - **Dopamine-2 (D2) Receptor Antagonism** in the GI tract → enhances gastric motility and accelerates gastric emptying (prokinetic effect). - **D2 Receptor Antagonism** in the **Chemoreceptor Trigger Zone (CRTZ)** → blocks emetic signaling (antiemetic effect). Because the CRTZ lacks a complete blood-brain barrier, domperidone can act here without entering the deeper CNS. - **Alpha-2 and Beta-2 Adrenergic Receptor Antagonism** → provides additional modulatory effects on stomach motility. - **Pituitary Gland Disinhibition** → Dopamine normally inhibits prolactin release. By blocking dopamine receptors, domperidone → increases **prolactin** secretion → stimulates milk production (galactagogue effect). This directly counteracts the dopamine-mimetic alkaloids found in toxic tall fescue.
動物種別の用量
- As a prokinetic agent · 0.05-0.1 mg/kg PO once or twice a day · PO · q12-24h · Scant clinical experience; suggested dose based upon experimental data.
- Antiemetic / Prokinetic · 0.1 - 0.5 mg/kg · PO · q8h-q12h · As needed · Administer 15-30 minutes before feeding.
- For fescue toxicity · 1.1 mg/kg PO once daily starting 10 to 15 days prior to Expected Foaling Date (EFD) · PO · q24h · Up to 5 days after foaling if inadequate milk · Treatment may be continued for up to 5 days after foaling if mares are not producing adequate milk.
- As a prokinetic agent · 0.05-0.1 mg/kg PO once or twice a day · PO · q12-24h · Scant clinical experience; suggested dose based upon experimental data.
- For vomiting due to gastritis · 2-5 mg (total dose) PO two to three times a day · PO · q8-12h
- Antiemetic / Prokinetic · 0.1 - 0.5 mg/kg · PO · q8h-q12h · As needed · Administer 15-30 minutes before feeding.
- Leishmaniasis (Treatment and Prevention) · 0.5 mg/kg · PO · sid · 28 days · For prevention, the 28-day course can be repeated every 3-4 months depending on infection risk.
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 domperidone
- Presence or suspicion of gastrointestinal obstruction, perforation, or hemorrhage
- Pregnant mares >15 days prior to expected foaling date (unless specifically managed)
- Horses intended for human consumption
- Gastrointestinal hemorrhage
- Mechanical GI obstruction or perforation
- Prolactin-secreting pituitary tumors (prolactinomas)
- Known hypersensitivity to the drug
有害事象
- Galactorrhea (inappropriate milk production)
- Gynecomastia
- Premature lactation in horses (dripping milk prior to foaling)
- Failure of passive transfer in foals
- Rarely: somnolence or dystonic reactions
- Arrhythmias (associated with withdrawn injectable human products, especially with hypokalemia or heart disease)
- Galactorrhea (milk production in females)
- Mammary gland hyperplasia
- Changes in estrus cycle
- Mild gastrointestinal upset
薬物相互作用
- Azole Antifungals (e.g., ketoconazole) · May increase domperidone levels due to metabolic inhibition.
- Anticholinergic Drugs · May reduce the gastrointestinal prokinetic efficacy of domperidone.
- Bromocriptine / Cabergoline · Domperidone may antagonize their dopamine-agonist effects on prolactin.
- Macrolide Antibiotics (e.g., erythromycin, clarithromycin) · May increase domperidone levels.
- Opioids · May reduce the gastrointestinal prokinetic efficacy of domperidone. · moderate
- Sustained-Release or Enteric-Coated Oral Medications · Domperidone may alter the absorptive characteristics of these drugs by decreasing GI transit times.
- Antacids · May decrease the oral absorption of domperidone · minor
- H2-receptor antagonists (e.g., famotidine) · May decrease the oral absorption of domperidone due to altered gastric pH · minor
- Ketoconazole · Inhibits CYP3A4 metabolism of domperidone, potentially increasing plasma concentrations and risk of QT prolongation · major
- Erythromycin · Inhibits CYP3A4 metabolism of domperidone, increasing plasma concentrations. · major
- Anticholinergics (e.g., Atropine) · May antagonize the gastrokinetic effects of domperidone. · moderate
- Antacids and H2 Blockers (e.g., Famotidine, Omeprazole) · Increase gastric pH, which may decrease the oral absorption of domperidone. Administer at least 2 hours apart. · moderate
モニタリング
- Clinical efficacy (resolution of vomiting, improved gastric emptying, or adequate milk production)
- Serum IgG concentrations in foals born to treated mares
- Serum prolactin levels (if indicated)
- Resolution of nausea and vomiting
- Improvement in clinical signs of Leishmaniasis (if used for this indication)
- Signs of galactorrhea, mammary enlargement, or false pregnancy in females
過量投与
There is no specific antidote for a domperidone overdose. - Employ standard gastrointestinal decontamination procedures if ingestion is recent and the patient is asymptomatic. - Provide supportive and symptomatic care as needed. Monitor for potential neurological signs (especially in MDR1-mutant dogs) or gastrointestinal upset.
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。