ジヒドロタキステロール
**ジヒドロタキステロール (DHT)** は、合成の脂溶性**ビタミンDアナログ**であり、獣医学においては主に副甲状腺機能低下症または重度の腎疾患に続発する低カルシウム血症の管理に使用されます。 歴史的に重要な薬物ですが、商業的な入手可能性の問題や、カルシトリオールのより好ましい薬物動態プロファイル（発現が早く作用時間が短いため、偶発的な高カルシウム血症の管理が容易）により、現在では臨床使用の大部分が**カルシトリオール**に取って代わられています。 重要な臨床的ポイント： * **作用発現**：エルゴカルシフェロール（ビタミンD2）より早いが、カルシトリオールよりは遅い。 * **腎臓での活性化をバイパス**：コレカルシフェロールとは異なり、DHTは活性化のために腎臓の1-α-ヒドロキシラーゼを必要としないため、重度の腎不全患者にも有効です。 * **毒性のリスク**：その効果が消失するまでに1〜3週間かかることがあるため、医原性高カルシウム血症の重大なリスクがあり、厳密なモニタリングが必要です。
作用機序: **Dihydrotachysterol** acts as a synthetic analog of 1,25-dihydroxyvitamin D. Its mechanism of action involves several key steps: * **Hepatic Activation**: DHT is absorbed from the GI tract and transported to the liver, where it undergoes hydroxylation by **hepatic 25-hydroxylase** → **25-hydroxydihydrotachysterol** (the active metabolite). * **Receptor Binding**: The active metabolite binds to **Vitamin D Receptors (VDR)** in target tissues (primarily intestine, bone, and kidneys). * **Calcium Homeostasis**: * **Intestine**: Stimulates the synthesis of calcium-binding proteins (e.g., calbindin) → significantly enhances dietary calcium and phosphorus absorption. * **Bone**: Works synergistically with parathyroid hormone (PTH) to promote the accretion and resorption of minerals, mobilizing calcium into the extracellular fluid. * **Kidneys**: Promotes the reabsorption of calcium by the renal tubules. > **Clinical Pearl**: Because the active form of DHT is structurally similar to 1,25-dihydroxyvitamin D, it effectively bypasses the need for **renal 1-alpha-hydroxylase**, an enzyme often deficient in chronic kidney disease.
動物種別の用量
- Hypocalcemia secondary to hypoparathyroidism · Initially give 0.03 mg/kg PO for several days or until effect is demonstrated, then give 0.02 mg/kg for 2 days, then 0.01 mg/kg per day. · PO · q24h · Pet should remain hospitalized until serum calcium concentration remains stable between 8-9.5 mg/dL. Recheck serum calcium on a weekly basis during early stages of treatment; recheck every 2-3 months long-term. Some dogs and cats that appear to be resistant to treatment on tablets or capsules may respond to the liquid form.
- Chronic hypocalcemia with oral calcium tx · Initially: 0.02-0.03 mg/kg/day PO. Maintenance: 0.01-0.02 mg/kg PO q24-48h. · PO · q24-48h
- Hypocalcemia secondary to hypoparathyroidism · Initially give 0.03 mg/kg PO for several days or until effect is demonstrated, then give 0.02 mg/kg for 2 days, then 0.01 mg/kg per day. · PO · q24h · Pet should remain hospitalized until serum calcium concentration remains stable between 8-9.5 mg/dL. Recheck serum calcium on a weekly basis during early stages of treatment; recheck every 2-3 months long-term. Some dogs and cats that appear to be resistant to treatment on tablets or capsules may respond to the liquid form.
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
- Pre-existing hypercalcemia
- Vitamin D toxicity
- Malabsorption syndromes
- Abnormal sensitivity to the effects of vitamin D
有害事象
- Hypercalcemia (manifesting as polydipsia, polyuria, anorexia, vomiting, lethargy)
- Nephrocalcinosis (soft tissue mineralization)
- Hyperphosphatemia
薬物相互作用
- Calcium-containing phosphorus binding agents (e.g., calcium carbonate) · Use with vitamin D analogs may induce severe hypercalcemia.
- Corticosteroids · Can nullify the calcium-elevating effects of vitamin D analogs.
- Digoxin · Patients are highly sensitive to the arrhythmogenic effects of hypercalcemia; intensified monitoring is required.
- Verapamil · Patients are sensitive to the effects of hypercalcemia; intensified monitoring is required.
- Mineral oil · May reduce the amount of DHT absorbed from the GI tract.
- Sucralfate · May reduce the amount of DHT absorbed from the GI tract.
- Cholestyramine · May reduce the amount of DHT absorbed from the GI tract.
- Phenytoin · May induce hepatic enzyme systems and increase the metabolism of Vitamin D analogs, thus decreasing their activity.
- Barbiturates · May induce hepatic enzyme systems and increase the metabolism of Vitamin D analogs, thus decreasing their activity.
- Primidone · May induce hepatic enzyme systems and increase the metabolism of Vitamin D analogs, thus decreasing their activity.
- Thiazide diuretics · May cause hypercalcemia when given in conjunction with Vitamin D analogs.
モニタリング
- Serum calcium levels (closely/twice daily during initial treatment; at least 2-4 times yearly during maintenance)
- Serum phosphorus levels (particularly in renal failure patients)
- Calcium-phosphorus product (Ca x P)
過量投与
### Acute Toxicity Acute ingestions should be managed using established protocols for GI decontamination. **Orally administered mineral oil** may reduce absorption and enhance fecal elimination. ### Chronic Toxicity (Hypercalcemia) Hypercalcemia secondary to chronic dosing is a serious complication. 1. **Discontinue Therapy**: Immediately stop DHT and any exogenous calcium supplementation. 2. **Severe Hypercalcemia Management**: Administer **furosemide**, **calcium-free IV fluids** (e.g., 0.9% normal saline) to promote diuresis, urine acidification, and **corticosteroids** (which decrease intestinal calcium absorption and increase renal excretion). 3. **Monitoring**: Because of the long duration of action of DHT (usually one week and potentially up to 3 weeks), hypercalcemia may persist for an extended period. 4. **Re-initiation**: Restart DHT/calcium therapy at a reduced dosage with diligent monitoring only when serum calcium levels return to the normal range.
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。