Frågedatum: 1982-01-29
RELIS database 1982; id.nr. 3014, DRUGLINE
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Dokumentation av dos-serumnivå-biverkningar för penicillamin?



Fråga: Dokumentation av dos-serumnivå-biverkningar för penicillamin?

Sammanfattning: Penicillamine is empirically known to be of therapeutic value in rheumatoid arthritis. The clinical pharmacological documentation is extremely sparse. There is no documentation on pharmacokinetics or dose-concentration-effect relationship in a recent textbook of rheumatology (3).

Svar: The pharmacological action of D-penicillamine is attributed to the metal ion chelating effect in treatment for Wilsons disease and also for lead and mercury poisoning. The mechanism attributed to the effect in cystinuria is a thiol disulfide exchange reaction "converting cystine in the body to a mixed disulfide between cysteine and penicillamine" (1). It was thought that this thiol property could be of benefit in rheumatoid arthritis and the effect of the drug was shown as reviewed (1). Immunological effects were also discussed and an inhibition of immunoglobulin secreting cells has also been proposed (1). Very little information was given on kinetics in this meeting; there are analytical methods for the drug. Plasma concentrations are low and most of the drug is bound in plasma (1). In spite of the wide use of D-penicillamine in different clinical conditions, little is known about the relation between concentration and effects. One of the few studies in the field is that of van der Korst and coworkers (2).

Within a few hours after a single oral dose of 250 mg D-penicillamine, a serum peak value of 5 ug/ml was reached, accompanied by a simultaneous drop in the serum cysteine concentration in a patient with RA. With a single high oral dose of l000 mg D-penicillamine, serum peak values of 15-20 ug/ml were reached within 3-4 hours followed by a biphasic serum concentration decline. The drug administration was continued for a longer period, the concentration showed a further steady increase accompanied by further decrease in the serum cysteine level. In one case, treatment had to be stopped after 20 weeks because of thrombocytopenia which was preceeded by an increase in serum level of D-penicillamine. The suggested relationship between this side effect and the serum concentration of the drug, however, should be interpreted with caution.

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