Details
| Stereochemistry | ABSOLUTE |
| Molecular Formula | C5H11NO2S |
| Molecular Weight | 149.211 |
| Optical Activity | UNSPECIFIED |
| Defined Stereocenters | 1 / 1 |
| E/Z Centers | 0 |
| Charge | 0 |
SHOW SMILES / InChI
SMILES
CC(C)(S)[C@@H](N)C(O)=O
InChI
InChIKey=VVNCNSJFMMFHPL-VKHMYHEASA-N
InChI=1S/C5H11NO2S/c1-5(2,9)3(6)4(7)8/h3,9H,6H2,1-2H3,(H,7,8)/t3-/m0/s1
Penicillamine, sold under the trade names of Cuprimine among others, is a medication primarily used for treatment of Wilson's disease, cystinuria and active rheumatoid arthritis. Penicillamine is a chelating agent recommended for the removal of excess copper in patients with Wilson's disease. From in vitro studies which indicate that one atom of copper combines with two molecules of penicillamine. Penicillamine also reduces excess cystine excretion in cystinuria. This is done, at least in part, by disulfide interchange between penicillamine and cystine, resulting in formation of penicillamine-cysteine disulfide, a substance that is much more soluble than cystine and is excreted readily. Penicillamine interferes with the formation of cross-links between tropocollagen molecules and cleaves them when newly formed. The mechanism of action of penicillamine in rheumatoid arthritis is unknown although it appears to suppress disease activity. Unlike cytotoxic immunosuppressants, penicillamine markedly lowers IgM rheumatoid factor but produces no significant depression in absolute levels of serum immunoglobulins. Also unlike cytotoxic immunosuppressants which act on both, penicillamine in vitro depresses T-cell activity but not B-cell activity.
Approval Year
Targets
| Primary Target | Pharmacology | Condition | Potency |
|---|---|---|---|
Target ID: CHEMBL2363057 |
Conditions
| Condition | Modality | Targets | Highest Phase | Product |
|---|---|---|---|---|
| Primary | CUPRIMINE Approved UseCUPRIMINE is indicated in the treatment of Wilson's disease, cystinuria, and in patients with severe, active
rheumatoid arthritis who have failed to respond to an adequate trial of conventional therapy. Launch Date2.9116801E10 |
|||
| Primary | CUPRIMINE Approved UseCUPRIMINE is indicated in the treatment of Wilson's disease, cystinuria, and in patients with severe, active
rheumatoid arthritis who have failed to respond to an adequate trial of conventional therapy. Launch Date2.9116801E10 |
|||
| Primary | CUPRIMINE Approved UseCUPRIMINE is indicated in the treatment of Wilson's disease, cystinuria, and in patients with severe, active
rheumatoid arthritis who have failed to respond to an adequate trial of conventional therapy. Launch Date2.9116801E10 |
Cmax
| Value | Dose | Co-administered | Analyte | Population |
|---|---|---|---|---|
5.36 μg/mL |
500 mg single, oral dose: 500 mg route of administration: Oral experiment type: SINGLE co-administered: |
PENICILLAMINE plasma | Homo sapiens population: HEALTHY age: ADULT sex: FEMALE / MALE food status: FED |
|
8.04 μg/mL |
500 mg single, oral dose: 500 mg route of administration: Oral experiment type: SINGLE co-administered: |
PENICILLAMINE plasma | Homo sapiens population: HEALTHY age: ADULT sex: FEMALE / MALE food status: FASTED |
AUC
| Value | Dose | Co-administered | Analyte | Population |
|---|---|---|---|---|
73.19 μg × h/mL |
500 mg single, oral dose: 500 mg route of administration: Oral experiment type: SINGLE co-administered: |
PENICILLAMINE plasma | Homo sapiens population: HEALTHY age: ADULT sex: FEMALE / MALE food status: FED |
|
83.97 μg × h/mL |
500 mg single, oral dose: 500 mg route of administration: Oral experiment type: SINGLE co-administered: |
PENICILLAMINE plasma | Homo sapiens population: HEALTHY age: ADULT sex: FEMALE / MALE food status: FASTED |
T1/2
| Value | Dose | Co-administered | Analyte | Population |
|---|---|---|---|---|
5.37 h |
500 mg single, oral dose: 500 mg route of administration: Oral experiment type: SINGLE co-administered: |
PENICILLAMINE plasma | Homo sapiens population: HEALTHY age: ADULT sex: FEMALE / MALE food status: FED |
|
5.01 h |
500 mg single, oral dose: 500 mg route of administration: Oral experiment type: SINGLE co-administered: |
PENICILLAMINE plasma | Homo sapiens population: HEALTHY age: ADULT sex: FEMALE / MALE food status: FASTED |
Doses
| Dose | Population | Adverse events |
|---|---|---|
1 g 1 times / day multiple, oral (max) Recommended Dose: 1 g, 1 times / day Route: oral Route: multiple Dose: 1 g, 1 times / day Sources: Page: p.1200 |
unhealthy, 45+/-12 n = 66 Health Status: unhealthy Condition: Diffuse systemic sclerosis Age Group: 45+/-12 Sex: M+F Population Size: 66 Sources: Page: p.1200 |
Disc. AE: Proteinuria, Rash... AEs leading to discontinuation/dose reduction: Proteinuria (10.6%) Sources: Page: p.1200Rash Myasthenia gravis (1.5%) Thrombocytopenia Flu-like illness Stomatitis |
4 g 1 times / day multiple, oral (max) Recommended Dose: 4 g, 1 times / day Route: oral Route: multiple Dose: 4 g, 1 times / day Sources: Page: p.4 |
unhealthy Health Status: unhealthy Condition: Wilson's disease|Cystinuria Sources: Page: p.4 |
Disc. AE: Leukopenia, Thrombocytopenia... AEs leading to discontinuation/dose reduction: Leukopenia (5%) Sources: Page: p.4Thrombocytopenia (5%) Proteinuria Hematuria Glomerulonephritis membranous Nephrotic syndrome Goodpasture's syndrome (rare) Obliterative bronchiolitis (rare) Myasthenia gravis Pemphigus vulgaris Pemphigus foliaceus |
AEs
| AE | Significance | Dose | Population |
|---|---|---|---|
| Myasthenia gravis | 1.5% Disc. AE |
1 g 1 times / day multiple, oral (max) Recommended Dose: 1 g, 1 times / day Route: oral Route: multiple Dose: 1 g, 1 times / day Sources: Page: p.1200 |
unhealthy, 45+/-12 n = 66 Health Status: unhealthy Condition: Diffuse systemic sclerosis Age Group: 45+/-12 Sex: M+F Population Size: 66 Sources: Page: p.1200 |
| Proteinuria | 10.6% Disc. AE |
1 g 1 times / day multiple, oral (max) Recommended Dose: 1 g, 1 times / day Route: oral Route: multiple Dose: 1 g, 1 times / day Sources: Page: p.1200 |
unhealthy, 45+/-12 n = 66 Health Status: unhealthy Condition: Diffuse systemic sclerosis Age Group: 45+/-12 Sex: M+F Population Size: 66 Sources: Page: p.1200 |
| Flu-like illness | Disc. AE | 1 g 1 times / day multiple, oral (max) Recommended Dose: 1 g, 1 times / day Route: oral Route: multiple Dose: 1 g, 1 times / day Sources: Page: p.1200 |
unhealthy, 45+/-12 n = 66 Health Status: unhealthy Condition: Diffuse systemic sclerosis Age Group: 45+/-12 Sex: M+F Population Size: 66 Sources: Page: p.1200 |
| Rash | Disc. AE | 1 g 1 times / day multiple, oral (max) Recommended Dose: 1 g, 1 times / day Route: oral Route: multiple Dose: 1 g, 1 times / day Sources: Page: p.1200 |
unhealthy, 45+/-12 n = 66 Health Status: unhealthy Condition: Diffuse systemic sclerosis Age Group: 45+/-12 Sex: M+F Population Size: 66 Sources: Page: p.1200 |
| Stomatitis | Disc. AE | 1 g 1 times / day multiple, oral (max) Recommended Dose: 1 g, 1 times / day Route: oral Route: multiple Dose: 1 g, 1 times / day Sources: Page: p.1200 |
unhealthy, 45+/-12 n = 66 Health Status: unhealthy Condition: Diffuse systemic sclerosis Age Group: 45+/-12 Sex: M+F Population Size: 66 Sources: Page: p.1200 |
| Thrombocytopenia | Disc. AE | 1 g 1 times / day multiple, oral (max) Recommended Dose: 1 g, 1 times / day Route: oral Route: multiple Dose: 1 g, 1 times / day Sources: Page: p.1200 |
unhealthy, 45+/-12 n = 66 Health Status: unhealthy Condition: Diffuse systemic sclerosis Age Group: 45+/-12 Sex: M+F Population Size: 66 Sources: Page: p.1200 |
| Leukopenia | 5% Disc. AE |
4 g 1 times / day multiple, oral (max) Recommended Dose: 4 g, 1 times / day Route: oral Route: multiple Dose: 4 g, 1 times / day Sources: Page: p.4 |
unhealthy Health Status: unhealthy Condition: Wilson's disease|Cystinuria Sources: Page: p.4 |
| Thrombocytopenia | 5% Disc. AE |
4 g 1 times / day multiple, oral (max) Recommended Dose: 4 g, 1 times / day Route: oral Route: multiple Dose: 4 g, 1 times / day Sources: Page: p.4 |
unhealthy Health Status: unhealthy Condition: Wilson's disease|Cystinuria Sources: Page: p.4 |
| Glomerulonephritis membranous | Disc. AE | 4 g 1 times / day multiple, oral (max) Recommended Dose: 4 g, 1 times / day Route: oral Route: multiple Dose: 4 g, 1 times / day Sources: Page: p.4 |
unhealthy Health Status: unhealthy Condition: Wilson's disease|Cystinuria Sources: Page: p.4 |
| Hematuria | Disc. AE | 4 g 1 times / day multiple, oral (max) Recommended Dose: 4 g, 1 times / day Route: oral Route: multiple Dose: 4 g, 1 times / day Sources: Page: p.4 |
unhealthy Health Status: unhealthy Condition: Wilson's disease|Cystinuria Sources: Page: p.4 |
| Myasthenia gravis | Disc. AE | 4 g 1 times / day multiple, oral (max) Recommended Dose: 4 g, 1 times / day Route: oral Route: multiple Dose: 4 g, 1 times / day Sources: Page: p.4 |
unhealthy Health Status: unhealthy Condition: Wilson's disease|Cystinuria Sources: Page: p.4 |
| Nephrotic syndrome | Disc. AE | 4 g 1 times / day multiple, oral (max) Recommended Dose: 4 g, 1 times / day Route: oral Route: multiple Dose: 4 g, 1 times / day Sources: Page: p.4 |
unhealthy Health Status: unhealthy Condition: Wilson's disease|Cystinuria Sources: Page: p.4 |
| Pemphigus foliaceus | Disc. AE | 4 g 1 times / day multiple, oral (max) Recommended Dose: 4 g, 1 times / day Route: oral Route: multiple Dose: 4 g, 1 times / day Sources: Page: p.4 |
unhealthy Health Status: unhealthy Condition: Wilson's disease|Cystinuria Sources: Page: p.4 |
| Pemphigus vulgaris | Disc. AE | 4 g 1 times / day multiple, oral (max) Recommended Dose: 4 g, 1 times / day Route: oral Route: multiple Dose: 4 g, 1 times / day Sources: Page: p.4 |
unhealthy Health Status: unhealthy Condition: Wilson's disease|Cystinuria Sources: Page: p.4 |
| Proteinuria | Disc. AE | 4 g 1 times / day multiple, oral (max) Recommended Dose: 4 g, 1 times / day Route: oral Route: multiple Dose: 4 g, 1 times / day Sources: Page: p.4 |
unhealthy Health Status: unhealthy Condition: Wilson's disease|Cystinuria Sources: Page: p.4 |
| Goodpasture's syndrome | rare Disc. AE |
4 g 1 times / day multiple, oral (max) Recommended Dose: 4 g, 1 times / day Route: oral Route: multiple Dose: 4 g, 1 times / day Sources: Page: p.4 |
unhealthy Health Status: unhealthy Condition: Wilson's disease|Cystinuria Sources: Page: p.4 |
| Obliterative bronchiolitis | rare Disc. AE |
4 g 1 times / day multiple, oral (max) Recommended Dose: 4 g, 1 times / day Route: oral Route: multiple Dose: 4 g, 1 times / day Sources: Page: p.4 |
unhealthy Health Status: unhealthy Condition: Wilson's disease|Cystinuria Sources: Page: p.4 |
PubMed
| Title | Date | PubMed |
|---|---|---|
| D-penicillamine induced Goodpasture's syndrome in Wilson's disease. | 1975 May |
|
| [Intrahepatic cholestasis following treatment with penicillamine D and indomethacine]. | 1976 May 28 |
|
| Generalized myasthenia gravis following use of D-pencillamine in Wilson's disease. | 1999 Jun |
|
| In vitro inhibition of hematopoiesis in a patient with systemic sclerosis treated with D-penicillamine. | 1999 Nov |
|
| Chelation and intercalation: complementary properties in a compound for the treatment of Alzheimer's disease. | 2000 Jun |
|
| Divergent effects of ischemia/reperfusion and nitric oxide donor on TNFalpha mRNA accumulation in rat organs. | 2001 Apr |
|
| Interaction of co-expressed mu- and delta-opioid receptors in transfected rat pituitary GH(3) cells. | 2001 Apr |
|
| Effect of NO donors on protein phosphorylation in intact vascular and nonvascular smooth muscles. | 2001 Apr |
|
| Coexistence of zinc and iron augmented oxidative injuries in the nigrostriatal dopaminergic system of SD rats. | 2001 Feb 1 |
|
| Heterologous activation of protein kinase C stimulates phosphorylation of delta-opioid receptor at serine 344, resulting in beta-arrestin- and clathrin-mediated receptor internalization. | 2001 Feb 16 |
|
| Role of copper ions and cytochrome P450 in the vasodilator actions of the nitroxyl anion generator, Angeli's salt, on rat aorta. | 2001 Feb 2 |
|
| Nitric oxide donors regulate nitric oxide synthase in bovine pulmonary artery endothelium. | 2001 Jan |
|
| Vascular endothelial growth factor receptor-2-mediated mitogenesis is negatively regulated by vascular endothelial growth factor receptor-1 in tumor epithelial cells. | 2001 Jan |
|
| Interference of biocytin with opioid-evoked hyperpolarization and membrane properties of rat spinal substantia gelatinosa neurons. | 2001 Jan 12 |
|
| Osteopontin is a negative feedback regulator of nitric oxide synthesis in murine macrophages. | 2001 Jan 15 |
|
| Nitric oxide in the potassium-induced response of the rat middle cerebral artery: a possible permissive role. | 2001 Jan 19 |
|
| Stimulation by nitric oxide of gastric acid secretion in bullfrog fundic mucosa in vitro. | 2001 Mar |
|
| Involvement of cyclooxygenase-derived prostaglandin E2 and nitric oxide in the protection of rat pancreas afforded by low dose of lipopolysaccharide. | 2001 Mar |
|
| The Disability Index of the Health Assessment Questionnaire is a predictor and correlate of outcome in the high-dose versus low-dose penicillamine in systemic sclerosis trial. | 2001 Mar |
|
| Induction of radioresistance by a nitric oxide-mediated bystander effect. | 2001 Mar |
|
| Nitric oxide reduces energy supply by direct action on the respiratory chain in isolated cardiomyocytes. | 2001 May |
Sample Use Guides
In all patients receiving penicillamine, it is important that CUPRIMINE be given on an empty stomach, at least one hour before meals or two hours after meals, and at least one hour apart from any other drug, food, or milk.
Wilson's Disease: In the absence of any drug reaction, a dose between 0.75 and 1.5 g that results in an initial
24-hour cupriuresis of over 2 mg should be continued for about three months, by which time the most reliable
method of monitoring maintenance treatment is the determination of free copper in the serum. In patients who cannot tolerate as much as 1 g/day initially, initiating dosage with 250 mg/day, and
increasing gradually to the requisite amount, gives closer control of the effects of the drug and may help to
reduce the incidence of adverse reactions.
Cystinuria:The usual dosage of CUPRIMINE in the treatment of cystinuria is 2 g/day for adults, with a range of 1 to
4 g/day. For pediatric patients, dosage can be based on 30 mg/kg/day. The total daily amount should be divided
into four doses. If four equal doses are not feasible, give the larger portion at bedtime. If adverse reactions
necessitate a reduction in dosage, it is important to retain the bedtime dose.
Route of Administration:
Oral
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| Classification Tree | Code System | Code | ||
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WHO-ESSENTIAL MEDICINES LIST |
4.2
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NDF-RT |
N0000175713
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NCI_THESAURUS |
C1971
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WHO-ESSENTIAL MEDICINES LIST |
2.4
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WHO-VATC |
QM01CC01
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LIVERTOX |
NBK548246
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WHO-ATC |
M01CC01
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52-67-5
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DB00859
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200-148-8
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m8467
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7264
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CHEMBL1430
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GNN1DV99GX
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5852
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D010396
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Penicillamine
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PENICILLAMINE
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100000082481
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81549
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3378
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1121
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1501006
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7975
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SUB127001
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2081
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ACTIVE MOIETY
METABOLITE (PARENT)
SALT/SOLVATE (PARENT)
