PENICILLAMINE

Chemistry - A monothiol chelating agent that is a degradation product of penicillins, penicillamineoccurs as a white or practically white, crystalline powder with a characteristic odor. Penicillamine isfreely soluble in water and slightly soluble in alcohol and has pKa values of 1.83, 8.03, and 10.83.
Penicillamine may also be known as D-Penicillamine, beta, beta-Dimethylcysteine, or D-3-Mercaptovaline.

Storage, Stability, Compatibility

Penicillamine should be stored at room temperature (15-30°C). The capsules should be stored in tight containers and the tablets in well-closed containers.

Pharmacology - PENICILLAMINE

Penicillamine chelates a variety of metals, including copper, lead, iron, andmercury, forming stable water soluble complexes that are excreted by the kidneys.
Penicillamine also combines chemically with cystine to form a stable, soluble complex that can bereadily excreted.
Penicillamine has antirheumatic activity. The exact mechanisms for this action are not understood, but the drug apparently improves lymphocyte function, decreases IgM rheumatoid factor andimmune complexes in serum and synovial fluid.
Although penicillamine is a degradation product of penicillins, it has no antimicrobial activity.
Uses, Indications - Penicillamine is used primarily for its chelating ability in veterinary medicine. Itis the drug of choice for Copper storage-associated hepatopathies in dogs, and may be used for thelong-term oral treatment of lead poisoning or in cystine urolithiasis.
Although the drug may be of benefit in chronic hepatitis, doses necessary for effective treatmentmay be too high to be tolerated.

Pharmacokinetics - PENICILLAMINE

Penicillamine is well absorbed after oral administration and peak serum levelsoccur about one hour (in humans) after dosing. The drug apparently crosses the placenta, butotherwise little information is known about its distribution. Penicillamine that is not complexed witheither a metal or cystine is thought to be metabolized in the liver and excreted in the urine and feces.

Contraindications, Precautions, Reproductive Safety

Penicillamine is contraindicated in patients who have a history of penicillamine-related blood dyscrasias.
Penicillamine has been associated with the development of birth defects in offspring of rats given10 times the recommended dose. There are also some reports of human teratogenicity.

Adverse Effects, Warnings

In dogs, the most prevalent adverse effect associated with penicillamine is nausea and vomiting. If vomiting is a problem, attempt to alleviate by giving smaller dosesof the drug on a more frequent basis. Although food probably decreases the bioavailability of thedrug, many clinicians recommend mixing the drug with food or giving at mealtimes if vomitingpersists. Although thought to occur infrequently or rarely, fever, lymphadenopathy, skinhypersensitivity reactions, or immune-complex glomerulonephropathy may also potentially occur.

Overdosage, Acute Toxicity

No information located.

Drug Interactions

The amount of penicillamine absorbed from the GI tract may be reduced bythe concurrent administration of food, antacids, or iron salts.
Administration of penicillamine with gold compounds, cytotoxic or other immunosuppressant agents (e.g., cyclophosphamide, azathioprine, but not corticosteroids), orphenylbutazone may increase the risk of hematologic and/or renal adverse reactions.
Concomitant administration with 4-aminoquinoline compounds (e.g., chloroquine, quinacrine) may increase the risks of severe dermatologic adverse effects occurring.
Penicillamine may cause pyridoxine deficiency in humans, but this is not believed to occur indogs.
Drug/Laboratory Interactions - When using technetium Tc 99m gluceptate to visualize thekidneys, penicillamine may chelate this agent and form a compound which is excreted via thehepatobiliary system. This may result in gallbladder visualization which could confuse the results.