イホスファミド
イホスファミドは、シクロホスファミドに構造が類似した強力な**抗悪性腫瘍アルキル化剤**です。 - **プロドラッグ**: 薬理活性を示すには肝臓での活性化が必要です。 - **獣医学での用途**: 主に犬や猫のリンパ腫や軟部組織肉瘤（猫のワクチン関連肉腫など）の試験的治療プロトコルで使用されます。 - **毒性の警告**: 非常に毒性が高く、重篤な出血性膀胱炎や腎毒性を防ぐために、**メスナ**の併用と積極的な**生理食塩水による利尿**が必須です。
作用機序: Ifosfamide is a **cell-cycle phase nonspecific** alkylating agent. - **Activation**: As a prodrug, it is metabolized primarily by hepatic cytochrome P450 enzymes (and to a lesser extent in the lungs) → **ifosfamide mustard** (the primary active alkylating metabolite). - **Mechanism**: The active mustard metabolite forms covalent bonds with DNA → **cross-linking of DNA strands** → interferes with DNA replication and RNA transcription → disrupts nucleic acid function and induces cell death.
動物種別の用量
- Vaccine-related sarcomas · 900 mg/m2 every 3 weeks. Mesna bolus and saline diuresis (30 minutes at 18.3 mL/kg/hr) were first given, then ifosfamide and saline diuresis continued for 5 hours after ifosfamide administration completed. · IV · Every 3 weeks
- Neoplasia · Normal (0.9%) saline IV diuresis at a fluid rate of 6 times maintenance over 30 minutes. Ifosfamide 900 mg/m2 diluted to 20 mg/mL or less, IV over 20 minutes. Normal saline IV diuresis at 6 times maintenance over 5 hours. Mesna urothelial protectant at 1/5 the patient's calculated mg dose at time zero (immediately before ifosfamide administration), and repeated 2 and 5 hours after ifosfamide. This therapy may be repeated on a 21 day basis. · IV · Every 21 days
- Lymphomas and soft tissue sarcomas · Give IV saline at 18.3 mL/kg/hr for 6 hours. Give ifosfamide at 350 mg/m2 (if patient weighs less than 10 kg), 375 mg/m2 (if greater than 10 kg) IV during the second 30 minutes of the 6-hour infusion. Mesna at a dose of 20% of the ifosfamide dose is given as an IV bolus at the start of the IV infusion and again 2 and 5 hours after the ifosfamide infusion. Repeat every 3 weeks. · IV · Every 3 weeks · Requires saline diuresis and mesna
- Lymphomas and soft tissue sarcomas · 375 mg/m2 · IV · Every 21 days · Follow cat dose 'b' protocol for diuresis and mesna administration
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
- Hypersensitivity to ifosfamide
- Severely depressed bone marrow function
- Active hemorrhagic cystitis
有害事象
- Myelosuppression (neutropenia at 5-7 days, potentially delayed to 14-21 days; thrombocytopenia)
- Hemorrhagic cystitis (bladder epithelial damage)
- Nephrotoxicity (proximal and distal tubular damage, electrolyte abnormalities)
- Volume overload and pulmonary edema (secondary to required saline diuresis)
- Neurotoxicity (somnolence, confusion, coma, encephalopathy)
- Gastrointestinal effects (nausea, vomiting, anorexia)
- Hypersensitivity reactions
- Alopecia
- Abnormal liver function tests
薬物相互作用
- Benzodiazepines (diazepam, chlordiazepoxide, oxazepam) · May increase concentrations of active ifosfamide and increase toxicity (demonstrated in mice; clinical significance in veterinary patients undetermined)
- Cisplatin · Ifosfamide may enhance cisplatin-induced ototoxicity and nephrotoxicity
- Myelosuppressive drugs (chloramphenicol, flucytosine, amphotericin B, colchicine, other antineoplastics) · Additive myelosuppression
モニタリング
- CBC with platelets (baseline and before re-dosing)
- Renal function with electrolytes (baseline and before re-dosing)
- Urinalysis (baseline and periodic)
- Liver function (baseline and periodic)
- Other adverse effects (volume overload/pulmonary edema, neurotoxicity, GI toxicity)
- Efficacy
過量投与
There is limited information available on acute overdoses. Toxicity is expected to be an exacerbation of adverse effects seen at usual doses. No specific antidote (including mesna) is known; treatment is supportive. **Methylene blue** (50 mg in a ~2% aqueous solution IV over 5 minutes) has been suggested to treat ifosfamide-induced encephalopathy in humans.
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。