カルボプラチン
カルボプラチンは、獣医腫瘍学で広く使用されている第2世代の白金系抗悪性腫瘍薬です。主に様々な癌や肉腫の治療に使用され、特に断脚後の**犬の骨肉瘤**に対する補助療法として最もよく知られています。 **臨床的特徴と利点：** * **猫に対する安全性：** 前世代のシスプラチン（猫に致命的な肺水腫を引き起こす）とは異なり、カルボプラチンは比較的安全であり、猫の患者にも日常的に使用されます。 * **毒性の軽減：** カルボプラチンは一般的に「より穏やかな」白金系薬剤と見なされています。シスプラチンと比較して腎毒性や催吐性（嘔吐）のリスクが著しく低いため、治療前後の積極的な静脈内輸液による利尿を必要としません。 * **多様な投与経路：** 全身的な静脈内投与に加えて、体腔内（胸水）、動脈内、および病変内（馬のサルコイド、猫の鼻鏡扁平上皮癌）への応用も期待されています。
作用機序: Carboplatin acts as a **bifunctional alkylating agent**. * **Cellular Entry & Activation:** Once inside the cell, the drug undergoes aquation (water molecules replace the cyclobutanedicarboxylate leaving group), forming highly reactive, positively charged platinum complexes. * **DNA Crosslinking:** These active complexes bind covalently to nucleophilic sites on DNA (primarily the N7 position of guanine and adenine). * **Inhibition:** This binding creates **intra-strand and inter-strand crosslinks** in the DNA double helix, physically obstructing DNA polymerases and RNA polymerases. * **Apoptosis:** The resulting DNA damage inhibits DNA replication, RNA transcription, and protein synthesis, ultimately triggering apoptosis (programmed cell death). > **Note:** Carboplatin is **cell-cycle nonspecific**, meaning it can damage cells during any phase of the cell cycle, though cells are most vulnerable during the G1 and S phases.
動物種別の用量
- Antineoplastic · 300-350 mg/m2 · IV · every 3 weeks · Dosage may need adjustment in patients with reduced renal function.
- Neoplastic diseases (All uses) · 300 mg/m2 · IV · q3-4wk · As determined by oncology protocol · Injected into the side port of a freely running i.v. infusion of 0.9% NaCl over a 10-15 min period.
- Neoplastic diseases (Intrapleural/intraperitoneal) · 225-300 mg/m2 · Intrapleural/Intraperitoneal · As directed by specialist · As determined by oncology protocol · Diluted in 0.9% NaCl or 5% dextrose water over a 5-10 min period. Consult a veterinary oncology specialist before administering via this route.
- Adenocarcinoma · Intralesional use may be considered · Intralesional
- Antineoplastic · 180-260 mg/m2 · IV · every 3 weeks · Has also been administered intratumorally for nasal planum carcinomas.
- Neoplastic diseases (All uses) · 200 mg/m2 · IV · q3-4wk · As determined by oncology protocol · Injected into the side port of a freely running i.v. infusion of 0.9% NaCl over a 10-15 min period. Monitor for delayed/unpredictable side effects.
- Neoplastic diseases (Intrapleural/intraperitoneal) · 200-240 mg/m2 · Intrapleural/Intraperitoneal · As directed by specialist · As determined by oncology protocol · Diluted in 0.9% NaCl or 5% dextrose water over a 5-10 min period. Consult a veterinary oncology specialist before administering via this route.
投与経路
禁忌
- History of hypersensitivity to carboplatin or other platinum agents
- Severe bone marrow depression
- Pregnancy (fetotoxic and embryotoxic - Category D)
有害事象
- Bone marrow suppression (neutropenia, thrombocytopenia)
- Anorexia
- Vomiting (typically 2-4 days post-dose)
- Hepatotoxicity (elevated bilirubin and liver enzymes)
- Nephrotoxicity (less frequent than cisplatin)
- Neuropathies (rare)
- Ototoxicity (rare)
- Anaphylactoid reactions (rare)
- Hyperuricemia
薬物相互作用
- Aminoglycosides · Potential for increased risk of nephrotoxicity or ototoxicity. · major
- Cisplatin · Patients previously treated with cisplatin have an increased risk of developing neurotoxicity or ototoxicity after receiving carboplatin.
- Myelosuppressive drugs · The leukopenic or thrombocytopenic effects secondary to carboplatin may be enhanced.
- Radiation therapy · Potential for increased hematologic toxicity.
- Vaccines · Live or killed virus vaccines administered after therapy may have reduced efficacy. Carboplatin may also potentiate live virus vaccine replication and increase adverse effects.
- Nephrotoxic agents (e.g., NSAIDs, Amphotericin B) · Increased risk of cumulative nephrotoxicity. · major
- Vaccines (live) · May adversely affect the safety and efficacy of vaccinations due to immunosuppression. · major
- Radiotherapy · Potential to act as a radiosensitizer for patients receiving concomitant radiotherapy. · moderate
モニタリング
- CBC (Complete Blood Count) to monitor nadir
- Serum electrolytes
- Uric acid
- Baseline renal and hepatic function tests
過量投与
An overdose of carboplatin is expected to cause severe, aggravated effects associated with the drug's primary toxicities: **bone marrow suppression, nephrotoxicity, and hepatotoxicity**. * **Monitoring:** Closely monitor for neurotoxicity, ototoxicity, hepatotoxicity, and nephrotoxicity. * **Treatment:** Therapy is primarily supportive as no specific antidote is available. Plasmapheresis or hemodialysis could potentially be of benefit in rapidly removing the drug from systemic circulation.
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。