빈크리스틴

항종양제 - 빈카 알칼로이드

빈크리스틴은 일일초(*Catharanthus roseus*)에서 유래한 세포주기 특이적(M기) 항종양제입니다. 수의 종양학에서 매우 중요한 약물로, 주로 림프종과 같은 림프 및 조혈계 종양의 복합 화학요법(예: CHOP 프로토콜)에 사용됩니다. 주요 임상 특징: * **골수 억제 최소화**: 다른 많은 항암제(예: 유사체인 빈블라스틴)와 달리 표준 용량에서 골수 억제 작용이 적어 복합 프로토콜에서 매우 유용합니다. * **전염성 성기 종양(TVT)**: 개 TVT 치료 시 단일 약물로서 매우 높은 효능을 보입니다. * **면역 매개성 혈소판 감소증(IMT)**: 난치성 IMT 치료에 독특하게 사용됩니다. 거핵구의 분절을 촉진하여 혈소판이 순환계로 빠르게 방출되도록 합니다. * **발포제(조직 괴사 유발)**: 심각한 조직 괴사를 유발할 수 있는 발포제입니다. 치명적인 일출(혈관 외 유출) 손상을 방지하기 위해 완벽하게 장착된 카테터를 통한 엄격한 정맥 내 투여가 필수적입니다.

작용 기전: Vincristine is a cell-cycle specific agent that acts during the **M-phase** (mitosis). * **Antineoplastic Action**: It binds specifically to **tubulin** dimers → inhibits microtubule polymerization → prevents the formation of the mitotic spindle → arrests cell division in **metaphase**, ultimately leading to apoptosis. * **Metabolic Effects**: It interferes with amino acid metabolism by inhibiting glutamic acid utilization and preventing purine synthesis, citric acid cycle, and urea formation. * **Thrombocytosis**: The exact mechanism is unknown, but it is believed to stimulate megakaryocyte fragmentation, accelerating the release of platelets into the peripheral blood. * **Immunosuppression**: Exhibits mild immunosuppressive activity, which may contribute to its efficacy in immune-mediated conditions.

동물 종별 용량

Cats

Neoplastic diseases · 0.5-0.75 mg/m2 · IV · every 1-3 weeks · Dosed in mg/m2, NOT mg/kg. Consultation with an oncologist recommended.
Neoplastic diseases (particularly lymphoproliferative disorders) · See Appendix for chemotherapy protocols and conversion of body weight to body surface area. · IV · Not specified · Not specified · Must be administered i.v. through a carefully pre-placed catheter.

Horses

Neoplastic diseases · 0.5 mg/m2 (usually 2.5-3 mg total dose per horse) · IV · weekly · Often used in CAP protocol with cytarabine and cyclophosphamide.

Dogs

Neoplastic diseases (usually in combination protocols) · 0.5-0.75 mg/m2 · IV · every 1-2 weeks · Dosed in mg/m2, NOT mg/kg. Consultation with an oncologist recommended.
Transmissible venereal tumor (TVT) · 0.5 mg/m2 (maximum dose 1 mg) · IV · once weekly · for 4-6 weeks · Used as sole therapy.
Adjunctive treatment of immune-mediated thrombocytopenia (IMT) · 0.5 mg/m2 · IV · once · If platelet count <10-20,000 cells/mcL or bleeding; consider bone marrow aspiration to document megakaryocytes.
Adjunctive treatment of immune-mediated thrombocytopenia (IMT) refractory to prednisone · 0.5-0.7 mg/m2 · IV · once · Given as an IV bolus or as an infusion over 4-6 hours.
Adjunctive treatment of immune-mediated thrombocytopenia (IMT) · 0.02 mg/kg · IV · once · Generally single use.

투여 경로

금기

Preexisting neuromuscular disease
Severe leukopenia
Uncontrolled infection
No specific absolute contraindications listed, but requires extreme caution in specific disease states

이상반응

Peripheral neuropathy (proprioceptive deficits, spinal hyporeflexia)
Paralytic ileus and severe constipation
Mild leukopenia
Tissue necrosis and sloughing (if extravasated)
Anorexia, vomiting, diarrhea
Impaired platelet aggregation
Increased liver enzymes
Syndrome of inappropriate ADH secretion (SIADH)
Jaw pain
Alopecia
Stomatitis
Seizures
Pulmonary edema (rare, reported in cats)
Peripheral neuropathy
Ileus
GI tract toxicity

약물 상호작용

Asparaginase · Additive neurotoxicity may occur; less common if asparaginase is administered after vincristine.
Mitomycin · Severe bronchospasm has occurred in humans receiving mitomycin-C with Vinca alkaloids.
Amiodarone · Inhibits P-glycoprotein; may increase vincristine toxicity, especially in MDR1/ABCB1 mutant dogs.
Azole Antifungals (e.g., ketoconazole) · Inhibits P-glycoprotein; may increase vincristine toxicity.
Carvedilol · Inhibits P-glycoprotein; may increase vincristine toxicity.
Cyclosporine · Inhibits P-glycoprotein; may increase vincristine toxicity.
Diltiazem · Inhibits P-glycoprotein; may increase vincristine toxicity.
Erythromycin · Inhibits P-glycoprotein; may increase vincristine toxicity.
Clarithromycin · Inhibits P-glycoprotein; may increase vincristine toxicity.
Quinidine · Inhibits P-glycoprotein; may increase vincristine toxicity.
Spironolactone · Inhibits P-glycoprotein; may increase vincristine toxicity.
Tamoxifen · Inhibits P-glycoprotein; may increase vincristine toxicity.
Verapamil · Inhibits P-glycoprotein; may increase vincristine toxicity.

모니터링

Efficacy (tumor burden reduction or platelet count)
Peripheral neuropathic clinical signs (e.g., gait abnormalities, constipation)
Complete blood counts (CBC) with platelets
Liver function tests (prior to therapy and repeated as necessary)
Serum uric acid
Complete Blood Count (CBC) prior to each dose
IV catheter site for any signs of extravasation during administration
Gastrointestinal signs (monitoring for ileus or severe constipation)
Neurological exams (monitoring for peripheral neuropathy, e.g., dragging paws, loss of reflexes)

과용량

Vincristine has a narrow therapeutic index. * **Dogs**: The maximally tolerated dose is reported as 0.06 mg/kg every 7 days for 6 weeks. Toxicity signs include slight anemia, leukopenia, increased liver enzymes, and neuronal shrinkage in the peripheral and central nervous systems. * **Cats**: The lethal dose is reportedly 0.1 mg/kg. Toxic signs include weight loss, seizures, leukopenia, and general debilitation. A reported 10X overdose (5 mg/m2) resulted in death within 72 hours despite intensive care (including calcium folinate). * **Treatment**: Primarily supportive. Includes cardiovascular and hematologic monitoring, anticonvulsants for seizures, and prevention of ileus. Fluid restriction and loop diuretics may be needed to manage SIADH. Leucovorin calcium has been used in humans, but efficacy is unconfirmed.

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