フィトナジオン (ビタミンK1)
**フィトナジオン（ビタミンK1）**は、天然のビタミンK1と同一の合成脂溶性ビタミンです。獣医療において重要な解毒剤であり、主に**抗凝固性殺鼠剤**（ワルファリン、ブロディファクム、ブロマジオロンなど）の摂取による血液凝固障害を回復させるために使用されます。 主な臨床応用： * **抗凝固性殺鼠剤中毒：** 治療の要。第2世代の殺鼠剤は半減期が非常に長いため、多くの場合3〜4週間の継続的なビタミンK1の補充が必要です。 * **スイートクローバー中毒：** 反芻動物において、カビの生えたスイートクローバーによるジクマロール中毒の治療に使用されます。 * **肝疾患：** ビタミンKの吸収や利用が障害される急性肝不全や胆道閉塞の補助療法として使用されます。 * **スルファキノキサリン中毒：** この抗コクシジウム薬に関連する出血性疾患を回復させます。 > **臨床のポイント：** ビタミンK1（フィトナジオン）はこれらの中毒に有効ですが、ビタミンK3（メナジオン）は無効であり、毒性のリスクが高くなります。フィトナジオンが新しい凝固因子を合成するには6〜12時間かかります。したがって、活動性出血のある患者には、活性凝固因子を提供するために直ちに血漿または全血の輸血が必要です。
作用機序: Phytonadione is essential for the hepatic synthesis of **Vitamin K-dependent coagulation factors (Factors II, VII, IX, and X)**. * **Mechanism:** In the liver, inactive precursors of these factors require γ-carboxylation of their glutamic acid residues to become functional. This carboxylation is catalyzed by the enzyme **γ-glutamyl carboxylase**, which requires the reduced form of Vitamin K (Vitamin K hydroquinone) as a cofactor. * **The Vitamin K Cycle:** During carboxylation, Vitamin K is oxidized to Vitamin K epoxide. The enzyme **Vitamin K epoxide reductase (VKOR)** recycles the epoxide back to the active hydroquinone form. * **Anticoagulant Rodenticides →** inhibit VKOR, depleting active Vitamin K and halting the production of functional clotting factors. Exogenous phytonadione bypasses this blockade, providing the necessary substrate to resume factor synthesis.
動物種別の用量
- Adjunctive therapy of acute liver failure · 1-5 mg/kg PO or SC q24h · PO, SC · q24h
- Anticoagulant rodenticide toxicity (exposed but non-bleeding) · 1.25-2.5 mg/kg PO twice daily with a fatty meal · PO · q12h · 2-4 weeks
- Anticoagulant rodenticide toxicity (bleeding patient) · 2.5 mg/kg PO twice daily with a fatty meal · PO · q12h · minimum of 4 weeks
- Anticoagulant rodenticide toxicity (symptomatic) · Loading dose of 2.5-5 mg/kg PO, then 3-5 mg/kg PO divided twice daily · PO · q12h · 14 days (1st gen) or at least 30 days (2nd gen/unknown)
- Known 1st generation coumarin toxicity or vitamin K1 deficiency · initially 2.5 mg/kg s.c. in several sites, then 1-2.5 mg/kg in divided doses p.o. · SC/PO · q8-12h · 5-7 days · Administer SC initially, followed by oral maintenance.
- Known 2nd generation coumarin (brodifacoum) toxicity · initially 5 mg/kg s.c. in several sites, then 2.5 mg/kg p.o. · SC/PO · q12h · 3 weeks · Restrict activity for 1 week post-treatment. Re-evaluate coagulation status 3 weeks after cessation of treatment.
- Known inandione (diphacinone) or unknown anticoagulant toxicity · initially 2.5-5 mg/kg s.c. over several sites. Then 2.5 mg/kg p.o. divided · SC/PO · q8-12h · 3-4 weeks · Re-evaluate coagulation status 2 days after stopping therapy. If PT is elevated, continue therapy for 2 additional weeks. If normal, rest for 1 week.
- Liver disease (pre-biopsy) · 0.5-1.0 mg/kg · SC · q12h · 1-2 days · Re-evaluate coagulation time before biopsy. If minimal improvement, fresh frozen plasma may be required.
投与経路
禁忌
- Known hypersensitivity to phytonadione or its components
- Hypoprothrombinemia due to hepatocellular damage (Vitamin K cannot correct this if the liver cannot synthesize the protein precursors)
- Intravenous administration (relative contraindication due to anaphylaxis risk)
- Known hypersensitivity to phytomenadione
- Intramuscular administration in severely coagulopathic patients (risk of severe hematoma)
有害事象
- Anaphylactoid reactions (especially following IV administration)
- Acute bleeding from the injection site (IM administration during early stages of treatment)
- Slow or poor absorption from SC or PO routes in hypovolemic patients
- Anaphylactic reactions (following IV administration)
- Haemolytic anaemia (in cats when overdosed)
- Anaphylaxis (primarily with IV administration)
- Injection site reactions (pain, swelling)
- Hematoma formation at injection sites (due to underlying coagulopathy)
薬物相互作用
- Oral Antibiotics · May decrease the numbers of Vitamin K-producing bacteria in the gut, though chronic therapy usually has no significant effect on phytonadione absorption.
- Mineral Oil · Concomitant oral administration may reduce the GI absorption of oral Vitamin K. · moderate
- Warfarin (and other coumarin/indanedione anticoagulants) · Phytonadione directly antagonizes the anticoagulant effects of these drugs.
- Phenylbutazone, Aspirin, Chloramphenicol, Sulfonamides, Diazoxide, Allopurinol, Cimetidine, Metronidazole, Anabolic Steroids, Erythromycin, Ketoconazole, Propranolol, Thyroid Drugs · May prolong or enhance the effects of anticoagulants, thereby antagonizing some of the therapeutic effects of phytonadione.
- Aspirin · Antagonizes the effects of vitamin K · moderate
- Chloramphenicol · Antagonizes the effects of vitamin K · moderate
- Allopurinol · Antagonizes the effects of vitamin K · moderate
- Diazoxide · Antagonizes the effects of vitamin K · moderate
- Cimetidine · Antagonizes the effects of vitamin K · moderate
- Metronidazole · Antagonizes the effects of vitamin K · moderate
- Erythromycin · Antagonizes the effects of vitamin K · moderate
- Itraconazole · Antagonizes the effects of vitamin K · moderate
モニタリング
- Clinical efficacy (resolution or lack of hemorrhage, pale mucous membranes, weakness)
- One-stage prothrombin time (OSPT / PT)
- Proteins Induced by Vitamin K Absence (PIVKA)
- International Normalized Ratio (INR)
- Prothrombin time (PT) is the best method of monitoring therapy
- Prothrombin Time (PT) - typically normalizes within 12-24 hours of starting therapy
- Activated Partial Thromboplastin Time (aPTT)
- PIVKA (Proteins Induced by Vitamin K Absence or Antagonism)
- Clinical signs of bleeding (mucous membranes, heart rate, respiratory rate)
過量投与
Phytonadione is relatively non-toxic. It is highly unlikely that toxic clinical signs would result after a single overdosage. However, inappropriate routes of administration (like rapid IV injection) can cause severe anaphylactoid reactions regardless of the dose.
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。