シスプラチン
**シスプラチン**は、獣医腫瘍学において主に犬の様々な癌や肉腫の治療、および馬の皮膚腫瘍の病変内注射に使用される白金系の重金属抗悪性腫瘍薬です。 **臨床上の重要なポイント：** * **催吐性が高い：** 化学受容器引き金帯（CTZ）を直接刺激します。投与前に強力な制吐薬（マロピタント、オンダンセトロン、ブトルファノールなど）を前投与することが標準的です。 * **腎毒性：** 腎尿細管の損傷を防ぐため、投与前、投与中、投与後に積極的な静脈内輸液による利尿（通常は0.9%生理食塩水）が必要です。 * **動物種特異性：** 致死的な用量依存性の原発性肺毒性を引き起こすため、**猫への投与は絶対禁忌**です。 * **取り扱い：** 危険な化学療法薬であるため、調製および投与中は厳格な安全プロトコル（手袋、防護服、閉鎖式薬物移送システムの着用）が必要です。
作用機序: Cisplatin acts as a **bifunctional alkylating agent**. * The **platinum** compound enters the cell and loses its chloride atoms in the low-chloride intracellular environment. * It then binds covalently to the N7 reactive center on **purine residues (guanine and adenine)** on the DNA. * This binding produces **interstrand and intrastrand crosslinks** in the DNA → alters DNA structure → inhibits DNA replication and transcription → leads to cell cycle arrest and **apoptosis**. * It is considered **cell cycle nonspecific**, though cells are most vulnerable during the G1 and S phases.
動物種別の用量
- For intralesional injection of skin tumors · 1 mg per cm3 of tumor/tumor bed intralesionally · Intralesional · at 2-week intervals · for 4 total treatments · Add 10 mg powder to 1 mL water and 2 mL medical-grade sesame oil (3.3 mg/mL). Inject in multiple planes no further than 0.6 to 1 cm apart.
- For potentially susceptible carcinomas and sarcomas · 30-70 mg/m2 (NOT mg/kg) IV over 20 minutes to several hours every 3-5 weeks · IV · every 3-5 weeks · Warning: Do not confuse cisplatin and carboplatin dosages; cisplatin dosages are much lower. Dogs must undergo saline diuresis before and after cisplatin therapy.
- Intracavitary administration for palliative control of neoplastic pulmonary effusions · 50 mg/m2 (NOT mg/kg) (diluted in normal saline to a total volume of 250 mL/m2) · Intracavitary · every 3-4 weeks as needed · Discontinue after 4th treatment if resolved completely · Give IV normal saline at 10 mL/kg/hr for 4 hours prior. Warm solution to body temp. Remove pleural fluid first, then slowly infuse.
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 (causes fatal pulmonary edema and dyspnea)
- Preexisting significant renal impairment
- Preexisting myelosuppression
- History of hypersensitivity to platinum-containing compounds
- Caution in patients with congestive heart failure (due to required fluid loading)
有害事象
- Severe vomiting (acute and delayed)
- Nephrotoxicity (renal tubular damage)
- Myelosuppression (thrombocytopenia, granulocytopenia)
- Ototoxicity (high-frequency hearing loss, tinnitus)
- Anorexia
- Diarrhea (including hemorrhagic)
- Seizures
- Peripheral neuropathies
- Electrolyte abnormalities
- Hyperuricemia
- Increased hepatic enzymes
- Anaphylactoid reactions
- Death
薬物相互作用
- Aminoglycosides · Potential for increased risk for nephrotoxicity; if possible, delay aminoglycoside administration by at least two weeks after cisplatin.
- Amphotericin B · Potential for increased risk for nephrotoxicity; if possible, delay amphotericin B administration by at least two weeks after cisplatin.
- Furosemide (and other loop diuretics) · Potential for increased ototoxicity.
- Phenytoin · Cisplatin may reduce serum levels of phenytoin.
モニタリング
- Urinalysis, BUN, and serum creatinine (baseline and before each dose)
- Hemogram and platelet count (baseline and before each dose)
- Serum electrolytes and acid-base status
- Tumor measurement and radiography (at least monthly to assess efficacy)
- Monitor for signs of vomiting, dehydration, or ototoxicity
過量投与
The minimum lethal dose of cisplatin in dogs is reportedly **2.5 mg/kg (≈80 mg/m2)**. Because of the potential for serious toxicity (severe nephrotoxicity, myelosuppression, intractable vomiting, and death), dosage calculations must be checked thoroughly. Overdose management involves aggressive IV fluid diuresis, antiemetics, and supportive care for bone marrow suppression.
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。