ミコフェノール酸モフェチル
**ミコフェノール酸モフェチル（MMF）**は強力な**免疫抑制薬**であり、獣医療においてステロイド節減薬として、または重度で難治性の免疫介在性疾患のレスキュー療法として利用されることが増えています。 主な臨床応用： * **免疫介在性溶血性貧血（IMHA）** * **糸球体腎炎** * **重症筋無力症** * **落葉状天疱瘡** * 臓器移植の拒絶反応抑制プロトコル 炎症性腸疾患（IBD）への使用も提案されていますが、犬における主な副作用が消化器症状（胃炎、下痢、腸炎）であるため、使用は複雑です。**臨床のポイント：** MMFは作用発現が比較的早いため、重篤な症例ではアザチオプリンよりも優先されることがありますが、高価であることと重度の消化器系副作用が制限要因となります。猫での使用経験は非常に限られており、猫はグルクロン酸抱合経路が欠損しているため、極めて慎重に使用する必要があります。
作用機序: **Mycophenolate mofetil (MMF)** is a prodrug that is rapidly hydrolyzed *in vivo* to its active form, **mycophenolic acid (MPA)**. * MPA non-competitively and reversibly inhibits **inosine monophosphate dehydrogenase (IMPDH)**. * **IMPDH** is the rate-limiting enzyme in the *de novo* synthesis of guanosine nucleotides. * Because T-lymphocytes and B-lymphocytes are highly dependent on this *de novo* purine synthesis pathway (and lack the purine salvage pathways utilized by other cell types), MPA selectively inhibits their proliferative responses. * This leads to → suppression of B-cell antibody formation and → inhibition of leukocyte recruitment to inflammatory sites and allotransplant tissues.
動物種別の用量
- IMHA · 10 mg/kg PO q12h · PO · q12h · Use with caution due to feline glucuronidation deficiency.
- Immune-mediated hemolytic anemia (IMHA) · 12-17 mg/kg PO once daily or divided twice daily · PO · q12-24h · Given with prednisolone (at 2 mg/kg q12-24h). Dogs also received ranitidine and sucralfate in the study.
- IMHA, myasthenia gravis or glomerulonephritis · 12-17 mg/kg PO once daily or divided twice daily · PO · q12-24h · Given with prednisone (at 2.2 mg/kg q12-24h).
- Immune-mediated hemolytic anemia (IMHA) · 400-600 mg/m2 orally twice daily · PO · q12h · Extrapolated from human medicine. Gastrointestinal side effects are common and dose limiting.
- Adjunctive treatment of glomerulonephritis · 10-20 mg/kg PO q12h · PO · q12h · 3-4 weeks trial · Trial of single drug therapy for 3-4 weeks recommended.
- Pemphigus foliaceous · 22-39 mg/kg/day divided into 3 daily doses · PO · q8h · Success rates of approx 50%; most dogs require glucocorticoids to control signs.
- Pemphigus foliaceous · 20-40 mg/kg/day PO divided q8h · PO · q8h · Steroid-sparing only.
- Aplastic anemia · 10 mg/kg PO q12h · PO · q12h · First effects observed 2 weeks later; complete remission in approx 3 weeks.
- Rescue agent for generalized myasthenia gravis · 500 mg (15-20 mg/kg) diluted and given IV over 2-4 hours · IV · q24h · 13 days · Given daily IV until swallowing oral meds, then switched to 10-11 mg/kg PO q12h.
投与経路
禁忌
- Documented hypersensitivity to mycophenolate
- Pregnancy (teratogenic effects noted in animal models)
- Caution in patients with severe renal dysfunction (dosage adjustment may be required)
- Caution in cats (deficient in glucuronidation metabolism)
- Pre-existing bone marrow suppression
- Pre-existing infections
有害事象
- Diarrhea (can be severe)
- Vomiting
- Anorexia
- Lethargy / reduced activity
- Weight loss
- Lymphopenia
- Increased rates of dermal infections
- Increased susceptibility to systemic infections
- Potential increased risk of malignancy/lymphoma
- Bone marrow suppression
- Nausea
- Diarrhoea
- Increased incidence of infections (e.g., pyoderma, Malassezia)
- Increased risk of lymphoma (reported in humans)
- Headache (reported in humans)
- Hypertension (reported in humans)
薬物相互作用
- Acyclovir · Increased serum concentrations of acyclovir and the phenolic glucuronide of mycophenolic acid
- Antacids (aluminum or magnesium containing) · Decreased absorption of mycophenolate; separate dosing by at least 2 hours
- Aspirin (or other salicylates) · Potentially increased concentrations of free mycophenolic acid
- Azathioprine · Increased risk for bone marrow suppression; use together not recommended in humans
- Iron (oral) · Decreased absorption of mycophenolate; separate dosing by at least 2 hours
- Probenecid · Potentially increased serum levels of mycophenolic acid and the phenolic glucuronide of mycophenolic acid
- Vaccines (live virus) · May be less effective; avoid use
- Drugs undergoing active renal tubular secretion · Competes for secretion, resulting in increased concentrations of either drug · moderate
- Antacids (e.g., omeprazole) · Concomitant administration may decrease the absorption of mycophenolate · moderate
モニタリング
- Clinical efficacy (resolution of immune-mediated disease signs)
- Complete Blood Count (CBC) for bone marrow suppression
- Renal and hepatic function panels
- Serum electrolytes
- Gastrointestinal effects (monitor weight, appetite, and client reports of vomiting/diarrhea)
- Complete Blood Count (CBC) to monitor for bone marrow suppression
- Gastrointestinal signs (nausea, vomiting, diarrhea)
- Signs of secondary infections (e.g., skin lesions, lethargy, fever)
過量投与
In oral acute studies performed in mice and monkeys, no deaths occurred in dosages up to 4,000 mg/kg and 1,000 mg/kg, respectively. In small animals, acute gastrointestinal disturbances (severe vomiting, diarrhea) could be expected. Treatment should be symptomatic and supportive.
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。