Penicillamine in Rheumatoid Disease: A Long-term Study

Day, A T; Golding, J.; P, Lee; Butterworth, Ann D.

doi:10.1136/bmj.1.5900.180

Cited by 113 publications

(19 citation statements)

References 3 publications

(1 reference statement)

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“…The 125 mg D-penicillamine group in our trial had a lower withdrawal rate (1 l%), although still higher than that seen in the placebo group (6%). It would appear that serious untoward effects are dose related, as has been stated by others (6,13). While a larger dose of D-penicillamine may result in greater efficacy, the risk of adverse reaction is also increased.…”

Section: Discussionmentioning

confidence: 54%

“…Trial entrants were required to have been previously treated with aspirin or another nonsteroidal antiinflammatory drug (NSAID) in therapeutic doses with inadequate control of their arthritis. They were required to have active disease as defined by 6 or more swollen joints and at least 2 of the following: 1) 9 or more tender joints on pressure, 2) 45 minutes or more of morning stiffness, 3) Westergren erythrocyte sedimentation rate of 28 m d h o u r or greater. One * The participating clinics and their directors represent 10 university-based centers and the National Institutes of Health and are as follows: Joseph G. Hardin, Jr., MD, University of Alabama, Birmingham; Harold E. Paulus, MD, University of California, Los patient in the 500 mg D-penicillamine group was inadvertently admitted into the study with only 4 swollen joints, but was eligible by all other criteria.…”

Section: Methodsmentioning

confidence: 99%

“…Early studies used 1,500 mg/day (l), and subsequent investigators have reported efficacy with reduced toxicity for 600 mg/day (2,6). Later, respected clinicians claimed that doses as low as 125, 250, and 500 mg of Dpenicillamine per day were effective (7,15,16).…”

mentioning

confidence: 99%

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Low‐Dose D‐Penicillamine Therapy in Rheumatoid Arthritis

Williams

Ward

Reading

et al. 1983

Arthritis & Rheumatism

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Section: Discussionmentioning

confidence: 54%

Section: Methodsmentioning

confidence: 99%

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Low‐Dose D‐Penicillamine Therapy in Rheumatoid Arthritis

Williams

Ward

Reading

et al. 1983

Arthritis & Rheumatism

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“…Treatment with PA has been reported to influence a number of immunological parameters during the course of RA. A consistent feature is the reduction in the amount of circulating immune com plexes in patients with RA (1)(2)(3).…”

Section: D-penicillaminementioning

confidence: 90%

Immunopharmacologic studies of D-penicillamine-L-cysteine disulfide.

Nakaike¹,

Tanaka²,

Tomita³

et al. 1983

Jpn.J.Pharmacol

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Abstract-Effects of D-penicillamine-L-cysteine disulfide (P-C) on some immunological parameters were examined in normal and immunity-impaired mice and rats. P-C enhanced the DNA synthesis in concanavalin A-stimulated mouse spleen cell cultures in vitro. In vivo, administration of P-C produced either enhancement or depression of plaque forming cell (PFC) response and delayed type hypersensitivity (DTH) to sheep red blood cells (SRBC) in low responder mice to SRBC, depending on the dose of P-C. P-C restored the impaired PFC response in hydrocortisone-pretreated mice. The enhancing effect of P-C was not shown in high responder mice to SRBC, but an in hibiting effect was observed. P-C inhibited the suppressor cell induction on PFC response in mice immunized with a supraoptimum dose of antigen. In adjuvant arthritic rats, P-C induced severe arthritis by eliminating the suppressor cells regulating this disease process. The relevance of these findings and mode of action of D-penicillamine in rheumatoid arthritis is discussed.

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“…The doses given to our patients were relatively low compared with those reported in some other experimental and clinical reports. Because we prefer the "go low, go slow" policy for D-penicillamine treatment (14) and because D-penicillamine was prescribed in the majority of patients for its therapeutic properties in suppressing disease activity in RA, higher doses were not appropriate.…”

Section: Tca Separation Techniquementioning

confidence: 99%

Interaction of D‐Penicillamine with Gold Salts

Davis

Barraclough

1977

Arthritis & Rheumatism

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Serum and urinary gold levels were monitored in 18 patients previously treated with gold salts for rheumatoid arthritis and the effects of D-peniCihnine studied. There was no statistically significant change in urinary gold levels on D-penicillamine therapy although there were some individual variations. Serum gold levels fell during D-penicillamine therapy but the rates of fall did not differ from those seen in patients not treated. In vitro studies on protein binding of gold salts suggest that a high affinity exists between gold salts and albumin with low levels of unbound gold even at concentrations far exceeding those seen in vivo. These preliminary results Suggest that at therapeutic levels only small amounts of gold are available for chelation by penicillamine. It is concluded that penicilldmine at low dosage is an unreliable chelator of gold salts in vivo and its use in the management of gold toxicity remains speculative.Both gold salts and D-penicillamine suppress disease activity in rheumatoid arthritis (RA) (1,2). The property of penicillamine by which this is mediated is not known, but this compound is a chelating agent and will influence the mobilization and excretion of heavy metals, particularly copper (3). Penicillamine will chelate with gold, although the evidence for this is based mainly on studies in experimental animals (4-6). Much of the supporting clinical data is based on individual case reports (7,8) and only a few studies have reported experience with larger numbers of patients (4). Despite this, it is widely accepted that D-penicillamine may be of value in the chelation of gold salts and its use has been advocated in the management of patients with adverse reactions to chrysotherapy.It is our clinical practice to institute D-penicillamine therapy in patients with rheumatoid arthritis after gold therapy if an adverse reaction to gold salts occurs or if gold therapy fails to ameliorate disease a c h y . In view of the chelating properties of D-penicillamine, it is of potential importance to know its effect on the mobilization and excretion of gold salts in patients who had previously received gold therapy. This is particularly relevant in patients who had discontinued chrysotherapy because of an adverse reaction, since significant

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Penicillamine in Rheumatoid Disease: A Long-term Study

Cited by 113 publications

References 3 publications

Low‐Dose D‐Penicillamine Therapy in Rheumatoid Arthritis

Low‐Dose D‐Penicillamine Therapy in Rheumatoid Arthritis

Immunopharmacologic studies of D-penicillamine-L-cysteine disulfide.

Interaction of D‐Penicillamine with Gold Salts

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