Indication |
For treatment of Wilson's disease, cystinuria and active rheumatoid arthritis. |
Pharmacodynamics |
Penicillamine is a chelating agent used in the treatment of
Wilson's disease. It is also used to reduce cystine excretion in
cystinuria and to treat patients with severe, active rheumatoid
arthritis unresponsive to conventional therapy. Penicillamine is used as
a form of immunosuppression to treat rheumatoid arthritis. It works by
reducing numbers of T-lymphocytes, inhibiting macrophage function,
decreasing IL-1, decreasing rheumatoid factor, and preventing collagen
from cross-linking. Its use in Wilson's disease, a rare genetic disorder
of copper metabolism, relies on its binding to accumulated copper and
elimination through urine. |
Mechanism of action |
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. |
Absorption |
rapidly but incompletely |
Volume of distribution |
Not Available |
Protein binding |
>80% (bound to plasma proteins) |
Metabolism |
Hepatic |
Route of elimination |
Excretion is mainly renal, mainly as disulfides. |
Half life |
1 hour |
Clearance |
Not Available |
Toxicity |
Not Available |