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Proceedings of the Royal Society of... 1977
Review
Topics: Administration, Topical; Corneal Ulcer; Humans; Penicillamine
PubMed: 122682
DOI: No ID Found -
Clinical Pharmacokinetics Nov 1987Penicillamine exists as 2 stereoisomers, but only the D-isomer is used therapeutically. Its chemical reactivity derives from its functional groups, of which the thiol... (Review)
Review
Penicillamine exists as 2 stereoisomers, but only the D-isomer is used therapeutically. Its chemical reactivity derives from its functional groups, of which the thiol group seems the most important. It is difficult to determine penicillamine in biological fluids because of its instability, the presence of endogenous compounds with a thiol function, and the various chemical forms in which it occurs, namely reduced free penicillamine, penicillamine bound to proteins, and internal (P-S-S-P) and mixed (P-S-S-C) disulphides. The earliest assay methods (colourimetry, isotopic methods, gas-phase chromatography) were neither sensitive nor specific. High performance liquid chromatography with electrochemical detection has led to a more specific assay for D-penicillamine, with detection based on either derivatisation reactions or on electro-oxidisation of the thiol function. With dual-electrode detectors (Au/Hg) disulphides can be assayed directly. D-penicillamine is absorbed rapidly but incompletely (40 to 70%) in the intestine, with wide interindividual variations. Food, antacids and, in particular, iron reduce absorption of the drug. Its bioavailability is also dramatically decreased in patients with malabsorption states. The peak plasma concentration occurs at 1 to 3 hours after ingestion, regardless of dose, and is of the order of 1 to 2 mg/L after an oral dose of 250 mg; some investigators have reported a double peak in plasma, which is probably not due to an enterohepatic cycle. The concentration in plasma then decreases rapidly, generally following a biphasic curve. When long term treatment is discontinued, there is a slow elimination phase lasting 4 to 6 days, which suggests that there is a 'deep compartment' or 'slow pool of the drug reversibly bound to tissues', particularly the skin. This may explain the persistence of its therapeutic effect and the occurrence of undesirable side effects after treatment has been stopped. During long term treatment plasma concentrations are highly variable between individuals. They do not seem to be correlated with the activity or the toxicity of D-penicillamine in patients with rheumatoid arthritis. More than 80% of plasma D-penicillamine is bound to proteins, particularly albumin. The rest is mainly in the free reduced form or as disulphides. Only a small portion of the dose is metabolised in the liver to S-methyl-D-penicillamine. The route of elimination is mainly renal; disulphides represent the main compounds found in the urine. Faecal excretion corresponds mainly to the non-absorbed fraction of the drug.
Topics: Chromatography, High Pressure Liquid; Drug Interactions; Humans; Intestinal Absorption; Penicillamine
PubMed: 3319347
DOI: 10.2165/00003088-198713050-00003 -
Scandinavian Journal of Rheumatology 1978Two patients with classical rheumatoid arthritis developed myopathy during treatment with penicillamine. In both patients, electromyography and muscle biopsies were...
Two patients with classical rheumatoid arthritis developed myopathy during treatment with penicillamine. In both patients, electromyography and muscle biopsies were indicative of polymyositis. In one patient, muscle enzymes were not examined at the appropriate time; in the other patient muscle enzymes were raised. This latter patient also had a rash and, in the dermal epidermal junction of pathological skin, granular deposits of immunoglobulin and complement were found. The myopathy subsided in both patients after withdrawal of penicillamine.
Topics: Action Potentials; Arthritis, Rheumatoid; Dermatomyositis; Female; Humans; Middle Aged; Muscle Contraction; Muscles; Myositis; Penicillamine
PubMed: 705267
DOI: 10.3109/03009747809098847 -
British Medical Journal Jun 1979
Topics: Arthritis, Rheumatoid; Female; Humans; Middle Aged; Myotonia; Neuromuscular Diseases; Penicillamine
PubMed: 466063
DOI: 10.1136/bmj.1.6176.1464 -
Biopharmaceutics & Drug Disposition 1979
Review
Topics: Animals; Arthritis, Rheumatoid; Chelating Agents; Collagen Diseases; Humans; Intestinal Absorption; Liver Diseases; Penicillamine
PubMed: 399737
DOI: 10.1002/bdd.2510010205 -
Harefuah Mar 1994
Review
Topics: Animals; Autoimmune Diseases; Humans; Immune System; Penicillamine; Penicillins
PubMed: 8194790
DOI: No ID Found -
Zeitschrift Fur Rheumatologie 1988D-penicillamine (DPA) leads to side effects in different ways: collagen and elastin crosslinking are inhibited, which results in thin and vulnerable skin, cutis laxa,... (Review)
Review
D-penicillamine (DPA) leads to side effects in different ways: collagen and elastin crosslinking are inhibited, which results in thin and vulnerable skin, cutis laxa, elastosis perforans serpiginosa, wound healing defects and embryopathy. Toxic influences effect thrombo- and leukocytopenia (incidence 5-15%), gastrointestinal disturbances (10-30%), changes or loss of taste (5-30%), loss of hair (1-2%), and partly proteinuria (5-20%). Acute hypersensitive reactions include DPA-allergy (2-10%). Severe adverse effects are autoimmune phenomena such as pemphigus, DPA-induced lupus erythematosus, polymyositis/dermatomyositis, membranous glomerulopathy and hypersensitivity pneumonitis (like Good-pasture's syndrome) and myasthenia (all less than 1%). In addition there are a number of rare side effects, often single observations. Risk factors include a genetic disposition (especially HLA-B8 and -DR3), poor sulphoxidizers and, to a certain degree, higher age. During pregnancy and in clinically relevant disturbances of bone marrow, liver and renal function DPA is contraindicated. The total incidence of side effects amounts to 30-60%, the withdrawal rate is 20-30%; therefore clear indications and a regular survey of DPA therapy are necessary.
Topics: Arthritis, Rheumatoid; Dose-Response Relationship, Drug; Humans; Penicillamine; Risk Factors
PubMed: 3063003
DOI: No ID Found -
Southern Medical Journal Oct 1981
Topics: Humans; Penicillamine
PubMed: 7292049
DOI: No ID Found -
Lancet (London, England) Nov 1981
Topics: Arthritis, Rheumatoid; Lymphocytes; Macrophages; Penicillamine
PubMed: 6118636
DOI: No ID Found -
Pharmacology & Therapeutics 1989