麥考酚酸酯
**麥考酚酸酯 (Mycophenolate mofetil, MMF)** 是一種強效的**免疫抑制劑**，在獸醫學中越來越常被用作類固醇替代藥物，或用於治療嚴重、難治性免疫介導疾病的救援療法。 主要臨床應用包括： * **免疫介導性溶血性貧血 (IMHA)** * **腎小球腎炎** * **重症肌無力** * **落葉型天皰瘡** * 器官移植抗排斥方案 雖然曾被建議用於炎症性腸病 (IBD)，但由於該藥物在犬隻的主要副作用為胃腸道症狀（胃炎、腹瀉和腸道發炎），因此使用上較為複雜。**臨床要點：** 在某些危重病例中，由於 MMF 作用相對迅速，常被優先於硫唑嘌呤 (azathioprine) 使用，但其高昂的成本和嚴重的胃腸道副作用可能成為限制因素。在貓的臨床經驗非常有限，且因貓缺乏葡萄糖醛酸結合代謝途徑，必須極度謹慎使用。
作用機制: **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.
各物種劑量
- 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.
給藥途徑
禁忌症
- 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
不良反應
- 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)
藥物相互作用
- 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
監測
- 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
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.
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