ペニシラミン
ペニシラミンは強力な**キレート剤**であり、獣医学においては主にベドリントンテリアやラブラドールレトリバーなどの**銅蓄積性肝疾患**の管理に使用されます。また、鉛や水銀中毒の長期経口治療、およびシスチン尿石症の溶解・予防にも有効です。抗線維化作用を持つため慢性肝炎に有益な可能性がありますが、必要な用量は耐容性が低いことが多いです。
作用機序: Penicillamine exerts its effects through multiple distinct mechanisms depending on the target condition: * **Heavy Metal Chelation**: Contains sulfhydryl groups that bind to heavy metals (copper, lead, iron, mercury) → forms stable, water-soluble complexes → facilitates rapid excretion via the kidneys. * **Cystine Urolithiasis**: Combines chemically with cystine via a disulfide interchange reaction → forms a stable, highly soluble penicillamine-cysteine mixed disulfide complex → readily excreted in urine, preventing stone formation. * **Antirheumatic Activity**: Mechanism is not fully elucidated, but it improves lymphocyte function and decreases **IgM rheumatoid factor** and immune complexes in serum and synovial fluid. * **Antifibrotic Activity**: Inhibits **lysyl oxidase** and collagen crosslinking → renders newly synthesized collagen more susceptible to enzymatic degradation.
動物種別の用量
- Lead poisoning · 125 mg q12h PO for 5 days. · PO · q12h · 5 days · After initial therapy with CaEDTA and if blood lead is greater than 0.2 ppm at 3-4 weeks post-treatment.
- Copper toxicity · 52 mg/kg daily for 6 days · PO · q24h · 6 days · FARAD recommends a minimum milk withdrawal time of 3 days after the last treatment and a 21-day preslaughter withdrawal.
- Copper toxicity · 26-52 mg/kg PO once daily for 6 days. · PO · q24h · 6 days
- Lead or mercury toxicity · 110 mg/kg PO for 1-3 weeks. · PO · Unknown · 1-3 weeks · Must clear GI tract of toxic metal before therapy.
- Adjunctive treatment of lead poisoning · 55 mg/kg PO q12h for 1-2 weeks. · PO · q12h · 1-2 weeks · Suggested to combine CaEDTA and penicillamine for several days until symptoms dissipate followed by a 3-6 week treatment with penicillamine.
- Lead or mercury toxicity · 110 mg/kg PO for 1-3 weeks. · PO · Unknown · 1-3 weeks · To prevent continued metal absorption, must clear GI tract of toxic metal before therapy. FARAD recommends a minimum milk withdrawal time of 3 days after the last treatment and a 21-day preslaughter withdrawal.
- Copper toxicity · 52 mg/kg daily for 6 days · PO · q24h · 6 days · FARAD recommends a minimum milk withdrawal time of 3 days after the last treatment and a 21-day preslaughter withdrawal.
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 a history of penicillamine-related blood dyscrasias
- Presence of lead in the gastrointestinal tract (can enhance absorption)
- Pregnancy (unless benefits outweigh teratogenic risks)
- Moderate to marked renal impairment
- History of penicillamine-related blood dyscrasias
有害事象
- Nausea
- Vomiting
- Depression
- Anorexia
- Dietary mineral deficiencies (zinc, iron, copper, calcium) with long-term use
- Fever (rare)
- Lymphadenopathy (rare)
- Skin hypersensitivity reactions (rare)
- Immune-complex glomerulonephropathy (rare)
- Teratogenicity
- Pyrexia
- Nephrotic syndrome
- Leucopenia (human data)
- Thrombocytopenia (human data)
- Lymphadenopathy (human data)
- Skin hypersensitivity reactions (human data)
薬物相互作用
- 4-Aminoquinoline drugs (e.g., chloroquine, quinacrine) · Concomitant administration may increase the risks for severe dermatologic adverse effects.
- Oral Cations (Zinc, Iron, Calcium, Magnesium) · May decrease the effectiveness of penicillamine if given orally together due to chelation in the gut.
- Food and Antacids · The amount of penicillamine absorbed from the GI tract may be reduced by concurrent administration.
- Gold Compounds · May increase the risk of hematologic and/or renal adverse reactions.
- Immunosuppressant drugs (e.g., cyclophosphamide, azathioprine) · May increase the risk of hematologic and/or renal adverse reactions.
- Phenylbutazone · May increase the risk of hematologic and/or renal adverse reactions.
- Antacids · Decreased gastrointestinal absorption of penicillamine · moderate
- Food · Decreased gastrointestinal absorption of penicillamine · moderate
- Iron salts · Decreased gastrointestinal absorption of penicillamine · moderate
- Zinc salts · Decreased gastrointestinal absorption of penicillamine · moderate
- Cytotoxic drugs · Increased renal and haematological adverse effects · major
- NSAIDs · Increased risk of renal damage · major
モニタリング
- Clinical efficacy (e.g., resolution of neurologic signs in lead poisoning)
- Liver enzymes (ALT) and liver copper levels via biopsy (for hepatopathy)
- Urinalysis and stone dissolution (for cystine urolithiasis)
- Complete blood count (CBC) and urinalysis to monitor for rare blood dyscrasias or glomerulonephropathy
- Full blood count (weekly initially)
- Urinalysis (weekly initially)
- Renal function
- Dietary mineral levels (zinc, iron, copper, calcium) during long-term use
過量投与
No specific acute toxic dose has been established for penicillamine. Toxic effects generally occur in patients taking the drug chronically. Any relationship of toxicity to dose is unclear; patients on small doses may develop toxicity. Management of overdose would be largely supportive and symptomatic.
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。