ストレプトゾシン
ストレプトゾシンは、元々*Streptomyces achromogenes*から分離された**抗悪性腫瘍抗生物質**ですが、市販品は合成的に製造されています。獣医学においては、主に膵臓のβ細胞に対する標的毒性を利用し、犬の**再発性、切除不能、または転移性のインスリノーマ**に対する重要な治療薬として使用されます。 * **臨床のポイント**: インスリノーマは過剰なインスリンを分泌する膵臓の機能性腫瘍であり、生命を脅かす低血糖を引き起こします。ストレプトゾシンはこれらの腫瘍細胞を選択的に破壊し、低血糖の制御と腫瘍の進行遅延に役立ちます。 * その重篤な毒性プロファイルのため、通常は外科的切除が不完全または不可能な難治性の症例に限定して使用されます。
作用機序: Streptozocin acts primarily as an **alkylating agent**. * **DNA Damage**: It cross-links DNA strands → inhibits **DNA synthesis** and prevents precursor incorporation into DNA. * **Beta-Cell Toxicity**: The drug enters cells via the **GLUT2 transporter**, which is highly expressed on pancreatic beta cells. Once inside, it causes a species-specific diabetogenic effect in dogs by reducing **nicotinamide adenine dinucleotide (NAD)** and ATP concentrations → irreversible beta cell necrosis. * While it possesses antibacterial activity against gram-positive and gram-negative bacteria, its severe cytotoxicity precludes its use as an antibiotic.
動物種別の用量
- Recurrent insulinoma after surgery (investigational) · Begin saline diuresis: Give normal saline at 18-20 mL/kg/hour for 7-8 hours. Over the 4th-5th hour, give streptozocin in the saline solution at a dose of 500 mg/m 2 IV. Give an antiemetic (e.g., butorphanol) at the end of the 7-hour period. · IV · Once · 7-8 hours total · Requires aggressive fluid therapy.
- Pancreatic islet cell tumors · Normal saline is given IV at 18.3 mL/kg/hr for 3 hours, then streptozocin is administered at 500 mg/m 2 over two hours with the saline diuresis continuing. After streptozocin infusion completed, continue saline diuresis for another 2 hours. Butorphanol is administered as an antiemetic immediately after streptozocin. · IV · May repeat at 3 week intervals · Until evidence of tumor progression, recurrence of hypoglycemia, or drug toxicity · Monitor for myelosuppression and nephrotoxicity.
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
- Patients without a confirmed histologic diagnosis of insulinoma
- Patients with completely resectable tumors
- Pregnancy (unless benefits outweigh risks; FDA Category C)
有害事象
- Serious, permanent renal toxicity
- Severe and protracted vomiting and nausea
- Mild myelosuppression
- Elevated liver enzymes
- Severe tissue necrosis if extravasated (vesicant)
薬物相互作用
- Doxorubicin · Streptozocin may prolong the half-life of doxorubicin; dosage adjustment may be required.
- Myelosuppressive drugs (e.g., carmustine) · Additive or synergistic myelosuppression may occur.
- Nephrotoxic drugs (aminoglycosides, amphotericin B, cisplatin) · May cause additive nephrotoxicity when used concurrently.
- Niacinamide (nicotinamide) · Can block the diabetogenic effects of streptozocin without altering its antineoplastic activity; this may be beneficial or detrimental depending on the clinical goal.
モニタリング
- Blood glucose (to assess efficacy)
- Baseline and post-treatment renal function tests (including urinalysis)
- CBC (for myelosuppression)
- Baseline and pre-retreatment liver function tests
- Hydration status (especially for the first few days after treatment or if vomiting is a problem)
過量投与
Severe toxicity may result if acutely overdosed, primarily manifesting as **acute renal failure**, **severe gastrointestinal distress**, and **myelosuppression**. Dosages must be calculated carefully based on body surface area (m^2). Treatment is supportive, focusing on aggressive fluid diuresis and management of uremia and cytopenias.
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。