プロベネシド
**プロベネシド (Probenecid)** は、主に**尿酸排泄促進薬**および**尿細管分泌阻害薬**として利用されるスルホンアミド誘導体です。 * **獣医学的用途**: 小型哺乳類での臨床使用は限られていますが、**爬虫類**の痛風（高尿酸血症）の管理において特に有用です。 * **薬理学的有用性**: 歴史的および薬理学的に、プロベネシドは弱有機酸、特に**β-ラクタム系抗生物質**（ペニシリンやセファロスポリン）の腎排泄を阻害する能力で有名です。これにより、これらの薬物の半減期を大幅に延長し、血清濃度を上昇させます。 * **臨床のポイント**: 犬において、プロベネシドはヒト（6.5時間）と比較して非常に長い消失半減期（約18時間）を持ちます。これは理論上、高価または急速にクリアランスされる薬物の投与間隔を延長するのに有利ですが、犬における確固たる臨床試験はまだ少ないのが現状です。
作用機序: Probenecid exerts its effects via competitive inhibition at the proximal renal tubules: * **Uricosuric Effect**: Competitively inhibits the **Urate Transporter 1 (URAT1)** on the apical membrane of the proximal tubule → prevents the reabsorption of uric acid from the urine back into the blood → enhances uric acid excretion and lowers serum urate levels. * **Secretion Inhibition**: Competitively inhibits **Organic Anion Transporters (OAT1, OAT3)** on the basolateral membrane → prevents the active tubular secretion of weak organic acids (e.g., penicillins, cephalosporins, NSAIDs) from the blood into the urine → prolongs the systemic half-life of these drugs.
動物種別の用量
- Gout · 250 mg PO q12h; can be increased as needed. · PO · q12h · Suggested dosage based upon human data as dose is not established for reptiles.
- Gout · 40 mg/kg PO q12h · PO · q12h
- Gout · 250 mg (total dose) PO twice daily; may increase as needed. · PO · twice daily
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
- Patients with or susceptible to uric acid renal or bladder calculus formation
- Urate nephropathy (e.g., cancer chemotherapy with rapidly cytolytic agents)
- Severe renal impairment (creatinine clearance < 30 mL/min)
- Gout in birds (can exacerbate the condition)
有害事象
- Headache (humans)
- Inappetence
- Nausea
- Mild vomiting
- Rashes
- Increased rate of gouty attacks initially (if no prophylaxis)
- Hypersensitivity (rare)
- Bone marrow suppression (rare)
- Hepatotoxicity (rare)
- Nephrotic syndrome (rare)
薬物相互作用
- Acyclovir · Increased acyclovir serum concentrations; probenecid can decrease renal excretion
- Antineoplastics (rapidly cytolytic) · Increased chance of uric acid nephropathy
- Aspirin (and other salicylates) · Salicylates antagonize the uricosuric effects of probenecid
- Benzodiazepines (lorazepam, oxazepam) · Probenecid may prolong action or reduce time for onset of action
- Beta-lactam antibiotics · Probenecid may increase serum concentrations by reducing renal excretion
- Beta-lactamase inhibitors (sulbactam, tazobactam) · Probenecid may increase serum concentrations by reducing renal excretion (does not affect clavulanic acid)
- Chlorpropamide · Probenecid decreases elimination; hypoglycemia is possible
- Ciprofloxacin/Enrofloxacin · Probenecid reduces renal tubular secretion of ciprofloxacin by about 50%. Significantly reduces renal excretion of enrofloxacin in goats.
- Dapsone · Possible accumulation of dapsone or its active metabolites
- Furosemide · Increased serum furosemide levels
- Heparin · Probenecid may increase and prolong heparin's effects
- Methotrexate · Probenecid may increase levels; increased risks for toxicity
モニタリング
- Serum uric acid
- Urine uric acid
- Acid-base balance (if concomitant urine alkalinization is used)
過量投与
Limited information is available in veterinary species. * **Human Data**: One massive (>45 g) overdose caused CNS stimulation, seizures, protracted vomiting, and respiratory failure. * **Management**: Handle initially using standardized protocols for removal of drug from the gut and preventing absorption. Treat supportively. Use caution co-administrating drugs that may compete with probenecid for tubular secretion. Consider contacting an animal poison control center for guidance.
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。