パミドロン酸二ナトリウム
**パミドロン酸二ナトリウム**は、獣医療において主に重度または難治性の**高カルシウム血症**（特にリンパ腫やアポクリン腺肛門嚢腺癌などの悪性腫瘍、およびコレカルシフェロール殺鼠剤やカルシポトリエンなどのビタミンDアナログ中毒に関連するもの）の管理に使用される第2世代の含窒素ビスホスホネート系薬剤です。 主な臨床応用： * **高カルシウム血症の管理**：標準治療（生理食塩水の静脈内投与、フロセミド、コルチコステロイド）が不十分な場合に、危険なほど高い血清カルシウム濃度を迅速に低下させます。 * **骨肉瘤および骨腫瘍**：微小転移を直接標的とする補助療法として研究されており、溶骨性病変に伴う重度の骨痛を軽減するための緩和薬として広く使用されています。 > **臨床上のポイント**：パミドロン酸は強力な骨吸収抑制剤であるため、血清カルシウムに対する影響は大きく、長期にわたります。急性腎毒性のリスクを最小限に抑えるため、カルシウムを含まない輸液で希釈し、ゆっくりと（通常2〜4時間かけて）静脈内点滴を行う必要があります。
作用機序: Pamidronate is a nitrogen-containing bisphosphonate that strongly binds to **hydroxyapatite crystals** in the bone matrix, specifically targeting areas of active bone turnover. * **Inhibition of Bone Resorption**: Once internalized by osteoclasts during bone resorption, pamidronate inhibits the enzyme **farnesyl pyrophosphate synthase (FPPS)** in the mevalonate pathway. * **Osteoclast Apoptosis**: Inhibition of FPPS prevents the prenylation of small GTPase proteins (like **Ras** and **Rho**) → disruption of osteoclast cytoskeletal function and ruffled border formation → **induction of osteoclast apoptosis**. * **Antineoplastic Effects**: In vitro, it exhibits direct cytotoxic and cytostatic effects on human osteosarcoma cell lines, potentially exerting antiangiogenic effects and inhibiting tumor cell migration.
動物種別の用量
- Control of hypercalcemia · 1.5-2 mg/kg IV over 4 hours · IV · From a retrospective study of 2 cats.
- Refractory hypercalcemia · 1 mg/kg IV given over 2 hours in 250 mL of normal saline · IV · every 4 weeks
- Control of hypercalcemia · 1.32 mg/kg in 150 mL of 0.9% saline with a 2 hour IV infusion · IV · can repeat in 1-3 weeks · Consider if parenteral saline, furosemide and corticosteroids do not resolve the issue.
- Treatment of cholecalciferol-induced toxicosis · 0.65-2 mg/kg in 0.9% NaCl · IV · on days 1 and 4 post-ingestion
- Attempting to reduce bone pain associated with osteosarcoma in combination with an NSAID · 1-2 mg/kg; diluted into 250 mL of 0.9% sodium chloride and administered as a CRI over 2 hours · IV · every 28 days
- Pain associated with skeletal neoplasias · 1-2 mg/kg IV over 2 hours · IV · every 21-28 days · Has been shown to provide pain relief in ~50% of dogs with skeletal neoplasia.
- Calcipotriene toxicosis · 1.3-2 mg/kg slow IV infusion · IV · single dose · In most cases, a single dose will lower calcium levels back to normal. Monitor calcium daily for at least 10 days after returning to normal.
- Control of hypercalcemia · 1.05-2 mg/kg IV over 4 hours · IV · From a retrospective study of 7 dogs.
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
- Hypersensitivity to pamidronate or other bisphosphonates
- Severe renal impairment (use with extreme caution; not tested in humans with serum creatinine > 5 mg/dL)
有害事象
- Electrolyte abnormalities (hypomagnesemia, hypocalcemia, hypophosphatemia)
- Cardiac arrhythmias (secondary to electrolyte shifts)
- Renal toxicity (especially with rapid infusion)
- Transient bone pain
- Anemia
- Thrombocytopenia
- Granulocytosis
- Ophthalmic syndromes (e.g., scleritis - reported in humans)
薬物相互作用
- Calcium-affecting drugs (e.g., furosemide, corticosteroids) · Can affect calcium levels; requires careful monitoring when used concurrently.
- Nephrotoxic drugs (e.g., cisplatin, aminoglycosides) · Potential for increased risk of nephrotoxicity; use with caution.
モニタリング
- Renal function (serum creatinine, BUN) and hydration status before treatment and prior to each dose
- Serum calcium (ionized preferred), phosphate, magnesium, and potassium
- CBC (baseline and continued if ongoing treatment)
- Urinalysis
過量投与
Overdosage of pamidronate may cause profound **hypocalcemia**, which can manifest clinically as muscle tremors, facial rubbing, seizures, or **tetany**. * **Treatment**: Should severe hypocalcemia occur, treat immediately with short-term, intravenous calcium supplementation (e.g., calcium gluconate) while monitoring the ECG.
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。