마이코페놀레이트 모페틸

면역억제제

**마이코페놀레이트 모페틸(MMF)**은 강력한 **면역억제제**로, 수의학에서 스테로이드 절약제 또는 중증 난치성 면역 매개 질환의 구제 요법으로 점점 더 많이 사용되고 있습니다. 주요 임상 적용 분야: * **면역 매개성 용혈성 빈혈(IMHA)** * **사구체신염** * **중증 근무력증** * **낙엽성 천포창** * 장기 이식 거부 반응 억제 프로토콜 염증성 장질환(IBD)에 대한 사용이 제안되기도 했으나, 개에서 이 약물의 주요 부작용이 위장관 증상(위염, 설사, 장염)이기 때문에 사용이 까다롭습니다. **임상 팁:** MMF는 작용 발현이 비교적 빠르기 때문에 일부 위급한 환자에서 아자티오프린보다 선호되는 경우가 많지만, 높은 비용과 심각한 위장관 부작용이 제한 요인이 될 수 있습니다. 고양이에서의 사용 경험은 매우 제한적이며, 고양이는 글루쿠론산 포합 대사 경로가 결핍되어 있으므로 극도로 주의하여 사용해야 합니다.

작용 기전: **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.

동물 종별 용량

Cats

IMHA · 10 mg/kg PO q12h · PO · q12h · Use with caution due to feline glucuronidation deficiency.

Dogs

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.

투여 경로

POIV

금기

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

이상반응

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)

약물 상호작용

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

모니터링

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)

과용량

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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