丙卡巴肼
**丙卡巴肼 (Procarbazine)** 是一種非典型的烷化抗腫瘤藥物，在獸醫學中主要作為 **MOPP** 或 **LOPP** 化療方案的一部分，用於治療犬貓的復發性或抗藥性淋巴瘤。 > **臨床要點**：與許多其他化療藥物不同，丙卡巴肼具有高度脂溶性，能輕易穿透**血腦屏障 (BBB)**。這項獨特屬性使其在治療中樞神經系統 (CNS) 腫瘤和發炎性疾病（尤其是犬的**肉芽腫性腦膜腦炎, GME**）方面具有極高的療效。 此外，丙卡巴肼具有微弱的**單胺氧化酶抑制劑 (MAOI)** 活性，因此在與其他藥物（如三環類抗憂鬱藥、擬交感神經藥）或特定飲食（富含酪胺的食物）併用時必須嚴格謹慎，以防止引發高血壓危象。
作用機制: Procarbazine is a prodrug that requires hepatic and renal metabolism to become active. Its exact mechanism is complex and multifaceted: - **Hepatic Metabolism** → Procarbazine is oxidized to **azo-procarbazine** and further metabolized to yield **methyl radicals** and **hydrogen peroxide**. - **DNA Alkylation** → The methyl radicals directly methylate nucleic acids, causing DNA strand breakage and inhibiting the synthesis of DNA, RNA, and proteins. - **Oxidative Stress** → The auto-oxidation process generates hydrogen peroxide, which directly induces oxidative damage to DNA. - **MAO Inhibition** → As an off-target effect, it inhibits the enzyme **monoamine oxidase (MAO)**, preventing the breakdown of monoamines like serotonin, norepinephrine, and dopamine.
各物種劑量
- MOPP lymphoma rescue · 50 mg/m2 or 10 mg (total dose per cat) · PO · once daily for the first 14 days of the treatment cycle · 14 days · Used as part of a protocol in combination with other antineoplastic agents.
- Lymphoma rescue (MOPP protocol) · 50 mg/m2 · PO · once daily for the first 14 days of the treatment cycle · 14 days · Used as part of a protocol in combination with other antineoplastic agents.
- Granulomatous meningoencephalitis (GME) · 25-50 mg/m2 · PO · once daily initially, then every other day · Initially given with prednisone treatment. After the first month, attempt to reduce to every other day. Monitor CBC weekly for the first month.
劑量為合格獸醫專業人員的臨床參考。請務必對照最新藥品仿單及個別病患確認。
給藥途徑
禁忌症
- Known hypersensitivity to procarbazine
- Inadequate bone marrow reserve
不良反應
- Nausea and vomiting
- Hepatotoxicity
- Myelosuppression (thrombocytopenia, leukopenia)
- Hemorrhagic gastritis
- CNS effects (sedation, agitation)
- Peripheral neuropathy (loss of tendon reflexes, paresthesias, myalgia)
藥物相互作用
- Alcohol/Ethanol · May cause severe nausea and vomiting (disulfiram-like reaction).
- CNS Depressant Drugs (barbiturates, opiates, antihistamines, phenothiazines) · Procarbazine can cause CNS depression; concurrent use can lead to severe depression. Coma and death have been reported with opiates.
- Foods with high tyramine content (aged cheese, yogurt) · Serious hypertension may result due to procarbazine's MAOI activity.
- Sympathomimetics (phenylpropanolamine, etc.) · Serious hypertension may result due to procarbazine's MAOI activity.
- Tricyclic Antidepressants (clomipramine, amitriptyline) · Do not use concurrently due to MAOI activity; risk of serotonin syndrome or hypertensive crisis.
監測
- Baseline: CBC, hepatic and renal function, urinalysis
- Repeat CBC at least once weekly for the first month of treatment, and then monthly thereafter
- Monitor for signs of neurotoxicity or severe GI distress
過量
The LD50 for laboratory animals ranges from 150 mg/kg (rabbits) to 1.3 grams/kg (mice). - **Treatment**: Treat overdoses aggressively to remove the drug from the gut if the overdose occurred within an hour or two (e.g., induction of emesis, activated charcoal). - **Anticipated Effects**: Extensions of the drug's adverse effect profile, including severe GI distress, profound bone marrow suppression, and CNS effects. - **Management**: Monitor closely and provide supportive care as necessary. Contact an animal poison control center for further guidance.
VetSheet 藥物參考供持牌獸醫專業人員作臨床決策輔助之用,不能取代專業判斷或廠方最新藥品說明書。