ドキソルビシン
**ドキソルビシン**は、小動物の獣医腫瘍学において最も広く使用されているアントラサイクリン系抗悪性腫瘍薬の一つです。その鮮やかな赤色と強力な副作用から、しばしば「赤い悪魔 (Red Devil)」と俗称されます。単剤または多剤併用プロトコルの一部として利用されます。 * **広範な有効性**: 犬および猫の**リンパ腫、癌腫、白血病、肉腫**など、さまざまな悪性腫瘍に対して高い効果を示します。 * **起源**: 元々は *Streptomyces peucetius* から分離されました。 * **臨床上のポイント**: 抗菌特性を持っていますが、その強力な細胞毒性のため、抗感染症薬としての使用は完全に除外されます。重度の**壊死起因物質 (vesicant)**であり、壊滅的な血管外漏出損傷を防ぐために、確実な静脈内アクセスの確保に細心の注意を払う必要があります。
作用機序: Doxorubicin is a cell-cycle non-specific cytotoxic agent with multiple mechanisms of action: * **Topoisomerase II Inhibition**: Intercalates between DNA base pairs and inhibits **topoisomerase II** → prevents DNA resealing → causes double-strand DNA breaks → triggers apoptosis. * **Macromolecular Synthesis Inhibition**: Directly inhibits DNA synthesis, DNA-dependent RNA synthesis, and protein synthesis. * **Free Radical Generation**: Undergoes electron reduction to form anthracycline semiquinone free radicals (often iron-mediated) → causes severe oxidative stress and lipid peroxidation. * **Clinical Pearl**: The heart is particularly susceptible to doxorubicin-induced oxidative damage because cardiac tissue has inherently low levels of **catalase**, an enzyme necessary to neutralize hydrogen peroxide. This is the primary mechanism behind its cumulative cardiotoxicity.
動物種別の用量
- Antineoplastic · 30 mg/m2 IV every 2-3 weeks · IV · every 2-3 weeks · Depending on the protocol used. Maximum cumulative dose = 240 mg/m2.
- Lymphoma, sarcomas, carcinomas · 30 mg/m2 (Use 1 mg/kg in dogs weighing <10 kg) · IV · q3wk · Maximum total cumulative dose not to exceed 240 mg/m2 · Administer over a minimum of 10 minutes into side port of freely running 0.9% NaCl.
- Antineoplastic · 20-30 mg/m2 IV every 2-4 weeks · IV · every 2-4 weeks · Depending on the protocol used. Maximum cumulative dose is usually 240 mg/m2.
- Lymphoma, soft tissue sarcomas · 1 mg/kg or 20-25 mg/m2 · IV · q3-5wk · Maximum total cumulative dose not to exceed 240 mg/m2 · Nephrotoxicity is a major risk in cats, especially at cumulative dosages >100 mg/m2.
- Antineoplastic · 30 mg/m2 IV every 3 weeks · IV · every 3 weeks · Depending on the protocol used.
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
- Pre-existing severe myelosuppression
- Impaired cardiac function
- Patients who have reached the total cumulative dose limit of doxorubicin and/or daunorubicin
- Cats with pre-existing renal insufficiency
有害事象
- Bone marrow suppression (nadir 5-10 days)
- Cardiac toxicity (acute arrhythmias and cumulative cardiomyopathy)
- Nephrotoxicity (particularly in cats)
- Gastroenteritis (anorexia, vomiting, diarrhea)
- Alopecia
- Stomatitis
- Immediate hypersensitivity/anaphylaxis (primarily in dogs)
- Severe tissue ulceration and necrosis (if extravasated)
薬物相互作用
- Antineoplastic agents, other · May potentiate the toxic effects of doxorubicin
- Calcium-channel blockers · Potentially could increase risk for cardiotoxicity associated with doxorubicin
- Carbamazepine · Decreased carbamazepine levels
- Cisplatin · Increased risk of toxicity for both agents; carefully weigh risks versus benefits
- Cyclophosphamide · May increase doxorubicin blood levels (AUC); doxorubicin may potentiate and prolong hematologic toxicity; coma and seizures have been reported in human patients · major
- Cyclosporine · Can increase doxorubicin and doxorubicinol (active metabolite) levels
- Glucosamine · May reduce doxorubicin effectiveness; use together not recommended in humans
- Phenytoin · Doxorubicin may decrease phenytoin levels
- Phenobarbital · May increase elimination and reduce blood levels of doxorubicin
- Streptozocin · May inhibit doxorubicin metabolism
- Verapamil · May increase doxorubicin levels
- Warfarin · Increased risk for bleeding
- Zidovudine · Increased risk for neutropenia
モニタリング
- Efficacy of tumor response
- CBC with platelets (monitor for myelosuppression, nadir at 5-10 days)
- ECG and/or echocardiogram (especially in dogs with pre-existing heart disease or predisposed breeds)
- Hepatic function prior to and during therapy
- Urinalysis, serum creatinine, and BUN (especially in cats due to nephrotoxicity risk)
過量投与
Inadvertent acute overdosage may be manifested by severe exacerbations of adverse effects (profound myelosuppression, severe GI toxicity, acute cardiotoxicity). A lethal dose for dogs has been reported as 72 mg/m2. **Treatment**: Supportive and symptomatic therapy is required. **Dexrazoxane** may be useful to help prevent cardiac toxicity and should be considered in cases of massive overdose.
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。