Adverse reactions to D-penicillamine after gold toxicity.

Dodd, Marylin; Griffiths, I. D.; Thompson, MF

doi:10.1136/bmj.280.6230.1498

Cited by 41 publications

(6 citation statements)

References 8 publications

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“…Some studies have shown a higher frequency of adverse effects induced by D-penicillamine in patients who had already had an adverse reaction with gold salts (Kean et al 1980;Smith et al 1982), especially protein-330 uria (Billingsley & Stevens 1981;Halla et al 1982) or medullary hypoplasia (Webley & Coomes 1979). Dodd et al (1980) found a higher frequency of adverse effects when D-penicillamine was prescribed less than 6 months after an adverse reaction occurring with gold. They suggested the hypothesis that, besides a cross reactivity, gold stored in the various tissues of the body was mobilised by formation of a gold-D-penicillamine complex.…”

Section: Pharmacokinetic Drug Interactionsmentioning

confidence: 96%

Clinical Pharmacokinetics of D-Penicillamine

Netter

Bannwarth

Pere

et al. 1987

Clinical Pharmacokinetics

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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.

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Section: Pharmacokinetic Drug Interactionsmentioning

confidence: 96%

Clinical Pharmacokinetics of D-Penicillamine

Netter

Bannwarth

Pere

et al. 1987

Clinical Pharmacokinetics

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“…Despite their dissimilar chemie al structures, the thiol compounds, sodium aurothiomalate and D-penicillamine, have remarkably similar clinical effects, and there is a marked similarity in incidence and type of adverse effects [140,169]. The association between prior gold nephropathy and D-penicillamine was discussed by several investigators.…”

Section: Prediction and Monitoring Of Development Of D-penicillamine mentioning

confidence: 96%

“…To predict D-penicillamine side effects, the association between side effects and various factors, such as HLA antigens [70,72,130,132,165,166], autoantibodies [167,168], and previous gold toxicity [103,140,169,170] has been studied. Wooley et al [70] investigated the possible relation between HLA antigens and toxicity of D-penicillamine and sodium aurothiomalate in rheumatoid arthritis patients.…”

Section: Prediction and Monitoring Of Development Of D-penicillamine mentioning

confidence: 99%

Nephrotoxicity of gold salts, D-penicillamine, and allopurinol

Ueda¹

1998

Clinical Nephrotoxins

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“…[14][15][16] It has been suggested that patients who have discontinued gold due to toxicity are more likely to develop adverse effects with penicillamine, possibly the same adverse effect which caused the cessation of gold, and appearing a relatively short period after starting penicillamine. This observation is controversial and indeed there has been a trial of combination therapy of gold and penicillamine which showed little substantial increase in toxicity, although the number of patients was small.!…”

Section: Penicillaminementioning

confidence: 98%

Slow-Acting Antirheumatic Drugs Drug Interactions of Clinical Significance

Munro

Sturrock

1995

Drug Safety

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The slow-acting antirheumatic drugs (SAARDs) are being used in an increasing proportion of patients with rheumatoid arthritis (RA). The potential toxicity of each drug is well recognised. Many patients with RA will be on other medications and the potential for adverse drug interactions with SAARDs is not so well publicised. There have, over the years, been numerous reports of possible drug interactions with SAARDs but few of these are clinically relevant. It is, however, vitally important that the physician is aware of a number of potentially life-threatening interactions, particularly those associated with methotrexate. The SAARDs are a very useful group of drugs for the treatment of RA and, by being aware of their potential toxicity and drug interactions, hopefully they can be used safely and effectively.

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Adverse reactions to D-penicillamine after gold toxicity.

Cited by 41 publications

References 8 publications

Clinical Pharmacokinetics of D-Penicillamine

Clinical Pharmacokinetics of D-Penicillamine

Nephrotoxicity of gold salts, D-penicillamine, and allopurinol

Slow-Acting Antirheumatic Drugs Drug Interactions of Clinical Significance

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