ダカルバジン
ダカルバジン（しばしば**DTIC**と呼ばれる）は、獣医腫瘍学において主に犬の再発性リンパ腫、軟部組織肉腫、およびメラノーマの治療に使用される注射用の**抗悪性腫瘍薬**です。 **臨床上のポイント：** * ダカルバジンは、細胞毒性を発揮するために肝臓での活性化を必要とする**プロドラッグ**です。 * 猫の肝臓がこの薬を活性型に十分に代謝できるかどうか不明であるため、**猫への使用は推奨されません**。猫における有効性と安全性は非常に予測困難です。 * 強力な**発泡薬（壊死起因物質）**であり、血管外漏出は重篤な組織壊死を引き起こす可能性があります。完全に留置された静脈カテーテルを介して、通常は希釈した上でゆっくりと点滴投与する必要があります。
作用機序: Dacarbazine is a prodrug that undergoes hepatic N-demethylation (likely via **cytochrome P450** enzymes) to form an active intermediate, which then degrades to form **reactive carbonium ions**. * **Alkylating Activity:** These carbonium ions act as alkylating agents → cross-link DNA strands → interfere with DNA transcription and replication. * **Antimetabolite Activity:** It also inhibits the incorporation of purine nucleosides into DNA. * It possesses minimal immunosuppressant activity and is generally considered **cell cycle-phase nonspecific**.
動物種別の用量
- Relapsed lymphoma, soft tissue sarcomas, melanoma · 800-1000 mg/m2 · IV · every 2-3 weeks · over 5-8 hours · NOT mg/kg. Depending on the protocol used.
- Relapsed Lymphoma (Rescue Protocol) · 800-1000 mg/m2 · IV · every 3 weeks · as determined by oncologist · Administer as a slow IV infusion (over several hours) to minimize adverse effects. Pre-medicate with antiemetics.
- Relapsed Lymphoma (Alternative schedule) · 200 mg/m2 · IV · sid · for 5 consecutive days · Repeat cycle every 3 weeks.
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
- Cats (due to unknown hepatic metabolism capabilities)
- Patients with known hypersensitivity to the drug
- Pregnancy (teratogenic)
- Pre-existing severe myelosuppression
- Severe hepatic dysfunction
- Pregnancy and lactation
- Known hypersensitivity
有害事象
- Severe gastrointestinal toxicity (vomiting, anorexia, diarrhea) - often dose-limiting
- Bone marrow suppression (leukopenia, thrombocytopenia) - nadir occurs several weeks post-treatment
- Severe tissue damage and pain (if extravasated)
- Venous spasm and phlebitis during IV administration
- Alopecia (rare)
- Hepatotoxicity (rare)
- Renal impairment (rare)
- Photosensitivity (rare)
- Severe nausea and vomiting
- Myelosuppression (neutropenia, thrombocytopenia)
- Tissue necrosis if extravasated
- Hepatotoxicity
- Lethargy
- Anorexia
薬物相互作用
- Myelosuppressive drugs (e.g., other antineoplastics, chloramphenicol, flucytosine, colchicine) · May cause additive myelosuppression when used concurrently with DTIC.
- Rifampin · May increase the hepatic metabolism of DTIC.
- Phenobarbital · May increase the hepatic metabolism of DTIC. · moderate
- Phenytoin · May increase the hepatic metabolism of DTIC.
- Other myelosuppressive agents · Additive bone marrow suppression · major
モニタリング
- Efficacy (tumor response)
- CBC with differential and platelets (monitor for myelosuppression)
- Renal function tests
- Hepatic function tests
- IV catheter site for signs of extravasation during infusion
- Complete Blood Count (CBC) prior to each dose and at nadir (typically 7-14 days post-treatment)
- Liver function tests (ALT, AST, Bilirubin)
- Renal function
- IV catheter site for signs of extravasation
- Gastrointestinal signs (vomiting, diarrhea)
過量投与
Because of the severe toxic potential of this agent, iatrogenic overdoses must be strictly avoided. Recheck all dosage calculations carefully (ensure dosing is based on body surface area in mg/m2, not mg/kg). Overdose will likely result in profound, life-threatening bone marrow suppression and severe gastrointestinal toxicity. Treatment is 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。