Details
| Stereochemistry | ABSOLUTE |
| Molecular Formula | C5H11NO2S.ClH |
| Molecular Weight | 185.6735 |
| Optical Activity | UNSPECIFIED |
| Defined Stereocenters | 1 / 1 |
| E/Z Centers | 0 |
| Charge | 0 |
SHOW SMILES / InChI
SMILES
CC(C)([C@]([H])(C(=O)O)N)S.Cl
InChI
InChIKey=CZDHUFYOXKHLME-DFWYDOINSA-N
InChI=1S/C5H11NO2S.ClH/c1-5(2,9)3(6)4(7)8;/h3,9H,6H2,1-2H3,(H,7,8);1H/t3-;/m0./s1
| Molecular Formula | ClH |
| Molecular Weight | 36.4609 |
| Charge | 0 |
| Count |
|
| Stereochemistry | ACHIRAL |
| Additional Stereochemistry | No |
| Defined Stereocenters | 0 / 0 |
| E/Z Centers | 0 |
| Optical Activity | NONE |
| Molecular Formula | C5H11NO2S |
| Molecular Weight | 149.2126 |
| Charge | 0 |
| Count |
|
| Stereochemistry | ABSOLUTE |
| Additional Stereochemistry | No |
| Defined Stereocenters | 1 / 1 |
| E/Z Centers | 0 |
| Optical Activity | UNSPECIFIED |
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 |
|---|---|---|
| [Myasthenia gravis and autoimmune thyroiditis during the treatment of rheumatoid polyarthritis withD-penicillamine. Anatomoclinical study of 1 case]. | 1976 Oct |
|
| [Extra-capillary glomerulonephritis induced by D-penicillamine therapy]. | 1999 Apr 3 |
|
| [D-penicillamine-induced pemphigus, polymyositis and myasthenia]. | 1999 Feb |
|
| Drug-associated antineutrophil cytoplasmic antibody-positive vasculitis: prevalence among patients with high titers of antimyeloperoxidase antibodies. | 2000 Feb |
|
| Nitric oxide in the afferent synaptic transmission of the axolotl vestibular system. | 2001 |
|
| Opposing actions of nitric oxide on synaptic inputs of identified interneurones in the central nervous system of the crayfish. | 2001 Apr |
|
| Induction of a non-rhythmic motor pattern by nitric oxide in hatchling Rana temporaria embryos. | 2001 Apr |
|
| Nitric oxide increases fluid extravasation from the splenic circulation of the rat. | 2001 Apr |
|
| Effect of NO donors on protein phosphorylation in intact vascular and nonvascular smooth muscles. | 2001 Apr |
|
| Cyclooxygenase-2 protein and prostaglandin E(2) production are up-regulated in a rat bladder inflammation model. | 2001 Apr 13 |
|
| Treatment of Wilson's disease: what are the relative roles of penicillamine, trientine, and zinc supplementation? | 2001 Feb |
|
| Coexistence of zinc and iron augmented oxidative injuries in the nigrostriatal dopaminergic system of SD rats. | 2001 Feb 1 |
|
| 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 attenuates H(2)O(2)-induced endothelial barrier dysfunction: mechanisms of protection. | 2001 Jan |
|
| Estradiol-induced attenuation of pulmonary hypertension is not associated with altered eNOS expression. | 2001 Jan |
|
| Cyclic AMP regulates the calcium transients released from IP(3)-sensitive stores by activation of rat kappa-opioid receptors expressed in CHO cells. | 2001 Jan |
|
| Nitric oxide regulates smooth-muscle-specific myosin heavy chain gene expression at the transcriptional level-possible role of SRF and YY1 through CArG element. | 2001 Jan |
|
| The regulation of NMDA-evoked dopamine release by nitric oxide in the frontal cortex and raphe nuclei of the freely moving rat. | 2001 Jan 19 |
|
| Metabolic regulation of aldose reductase activity by nitric oxide donors. | 2001 Jan 30 |
|
| [Drug-induced taste disorders: analysis of the French Pharmacovigilance Database and literature review]. | 2001 Jan-Feb |
|
| 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 |
|
| Transport of opioids from the brain to the periphery by P-glycoprotein: peripheral actions of central drugs. | 2001 Mar |
|
| L-arginine effects on Na+ transport in M-1 mouse cortical collecting duct cells--a cationic amino acid absorbing epithelium. | 2001 Mar 15 |
|
| Effect of redox modulation on xenogeneic target cells: the combination of nitric oxide and thiol deprivation protects porcine endothelial cells from lysis by IL-2-activated human NK cells. | 2001 Mar 15 |
|
| The role of delta-opioid receptor subtypes in neuropathic pain. | 2001 Mar 9 |
|
| Scleroderma in a child after chemotherapy for cancer. | 2001 Mar-Apr |
|
| Glutamate release via NO production evoked by NMDA in the NTS enhances hypotension and bradycardia in vivo. | 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
| Substance Class |
Chemical
Created
by
admin
on
Edited
Sat Jun 26 14:34:45 UTC 2021
by
admin
on
Sat Jun 26 14:34:45 UTC 2021
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| Record UNII |
5N9JK529ZJ
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| Record Status |
Validated (UNII)
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| Record Version |
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92173
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5N9JK529ZJ
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2219-30-9
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M8467
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218-727-9
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SUB03676MIG
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PARENT -> SALT/SOLVATE |
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ACTIVE MOIETY |