阿崙膦酸鈉
**阿崙膦酸鈉 (Alendronate sodium)** 是一種口服含氮雙膦酸鹽類藥物，主要用於抑制破骨細胞的骨吸收作用。 **主要臨床重點：** * **主要適應症：** 在獸醫學中用於治療難治性高血鈣症（例如貓的特發性高血鈣症、惡性腫瘤引起的高血鈣症）、貓破牙細胞性齒吸收病灶 (FORLs)，以及作為骨肉瘤或組織細胞肉瘤的輔助治療。 * **試驗性狀態：** 在小動物的臨床經驗仍然非常有限。劑量和安全性資料仍在建立中。 * **生物利用度挑戰：** 口服吸收率極差（<2%），且會因食物而大幅降低，需要嚴格的禁食計畫。 * **食道風險：** 已知在人類會引起嚴重的食道刺激和糜爛；在寵物中需要特定的給藥技巧（例如餵水、在嘴唇塗抹奶油）以確保藥物快速通過胃腸道。
作用機制: Alendronate is a nitrogenous bisphosphonate that strongly binds to **hydroxyapatite** crystals in the bone matrix. * **Mechanism:** During bone resorption, the drug is locally released and endocytosed by **osteoclasts**. * **Intracellular Pathway:** Inside the osteoclast, alendronate inhibits the enzyme **farnesyl pyrophosphate synthase (FPPS)** within the mevalonate pathway → prevents the prenylation (lipid modification) of small GTP-binding proteins (such as Ras, Rho, and Rab) → disrupts osteoclast cytoskeletal organization and ruffled border formation → induces osteoclast **apoptosis**. * **Secondary Effects:** By inhibiting osteoclastogenesis and promoting apoptosis, it indirectly reduces angiogenesis and may inhibit cancer cell proliferation in osteogenic neoplasms.
各物種劑量
- Feline odontoclastic resorptive lesions (FORLs) · 3 mg/kg · PO · q12h · Note: Use for this indication in cats is at present very controversial. (Plumb 2006)
- Idiopathic hypercalcemia (after dietary change has been attempted) · Initially 2 mg/kg. Most cats respond to 10 mg (total dose). · PO · once weekly · Administer at least 6 mL of water after administration and butter the lips to increase salivation and increase transit. If efficacious, effects usually seen in 3-4 weeks. Monitor via serum ionized calcium.
- Refractory hypercalcemia · 0.5-1 mg/kg · PO · once daily
- Investigational treatment of histiocytic sarcoma complex · Loading dose of 70 mg/m 2 (NOT mg/kg) · PO · daily for 14 days, then every other day for 14 days, then once weekly · Monitor for esophageal problems (excessive salivation, regurgitation).
劑量為合格獸醫專業人員的臨床參考。請務必對照最新藥品仿單及個別病患確認。
給藥途徑
禁忌症
- Esophageal abnormalities (e.g., strictures, achalasia) that delay esophageal emptying
- Inability to stand or sit upright for 30 minutes post-administration (human guideline; veterinary relevance is managed via water chasers/activity)
- Severe renal dysfunction (Creatinine Clearance < 35 mL/min)
- Known hypersensitivity to alendronate or other bisphosphonates
不良反應
- Upper GI irritation and erosions
- Esophageal stricture or ulceration
- Vomiting
- Inappetence
- Jaw osteonecrosis (rare but documented in humans)
- Musculoskeletal pain
- Hypocalcemia (with overdose)
- Hypophosphatemia (with overdose)
藥物相互作用
- Aspirin · Increased risk of upper GI adverse effects and erosions.
- Calcium-containing oral products or food · Likely to significantly decrease the already low oral bioavailability of alendronate.
- Ranitidine (IV) · Increased oral alendronate bioavailability two-fold in a human study.
- NSAIDs · Humans taking NSAIDs with alendronate had no higher rates of GI adverse reactions than when NSAIDs were used with placebo, though caution is still advised. · moderate
- Antacids (Aluminum, Magnesium, Calcium) · Significantly decreases alendronate absorption · major
- Iron supplements · Decreases alendronate absorption · major
監測
- Serum ionized calcium
- Serum phosphorus
- Serum potassium and sodium
- Signs of GI adverse effects (excessive salivation, regurgitation, dysphagia, inappetence)
過量
**Toxicity Profile:** No lethality was observed in dogs receiving doses up to 200 mg/kg. Lethality in rodents occurs at >550 mg/kg. **Clinical Signs of Overdose:** Hypocalcemia, hypophosphatemia, and severe upper GI reactions (ulceration, erosions). **Treatment:** * **DO NOT induce vomiting** due to the risk of severe esophageal irritation. * Administer **oral antacids or milk** immediately to bind the drug and prevent systemic absorption. * Monitor serum calcium and phosphorus levels closely. * Provide supportive care as needed.
VetSheet 藥物參考供持牌獸醫專業人員作臨床決策輔助之用,不能取代專業判斷或廠方最新藥品說明書。