Penicillamine disulphide

Disposition in the Body. Readily but incompletely absorbed after oral administration. About 50% of an oral dose is excreted in the urine in 48 hours with about 10% as unchanged drug, up to 25% as cysteine-penicillamine disulphide, about 15% as penicillamine disulphide, and less than 10% as 5 -methyl-D-penicillamine about 35% of an oral dose is eliminated in the faeces in 3 days. After intravenous administration, about 80% of the dose is excreted in the urine in 24 hours traces of penicillamine remain in the plasma after 48 hours due to protein binding. 

Heat-denatured IgG is inflammatory when fixed with complement. Gerber was the first to report that a mixture of penicillamine disulphide and Cu(II)sul-... 

Step 3 D-Penicillamine thus obtained is oxidised quantitatively by iodine to give rise to a disulphide, as expressed in the following equation whereas, the excess iodine is back titrated with 0.02 N sodium thiosulphate solution ... 

D-penicillamine is so named because it was first isolated as an amine, from the degradation products of penicillin by Abraham et al [87]. Later studies showed the characteristic chemical behavior of D-penicillamine which involve three types of reactions, formation of disulphide links, formation of thiazolidine rings, and formation of metal complexes and chelates [67]. It was first used in 1956 in the treatment of Wilson s disease [88]. D-penicillamine has since been used in the treatment of many diseases, such as cystinuria [89], rheumatoid arthritis [90-92], systemic sclerosis [93], primary bdiary cirrhosis [94], heavy metal poisoning due to lead [95], cadmium [%], and mercury [97], and hyperviscosity syndrome [99]. In rheumatoid arthritis, D-peni-cdlamine has been widely accepted as an effective second line treatment. Despite of its effectiveness, it causes many adverse effects, such as skin rashes [99,100], taste abnormalities [100,101], hepatic dysfunction [102-104], gastrointestinal toxiciiy [99,105], proteinuria [100,106], hematuria [107, 108], thrombocytopenia [92, 109], aplastic anemia [110], lupus-like syndrome [111, 112], Goodpasture s-tike pulmonary renal syndrome [113-115], vasculitis [116,117], myasthenia gravis [118-122], polymyositis [123, 124], and dermatomyositis [125]. 

Levine BB (1960 c) Formation of D-penicillamine-cysteine mixed disulphide by reaction of D-benzylpenicilloic acide with cysteine Nature 187 940 Levine BB (1961) Studies on the formation of the penicillin antigen. II. Some reactions of D-benzylpenicillenic acid in aqueous solution at pH 7.5. Arch Biochem Biophys 93 50 Levine BB (1962) N(a-D-penicilloyfamines as univalent hapten inhibitors of antibody-de-pendent allergic reactions to penicillin. J Med Chem 5 1025 Levine BB (1963) Studies on the dimensions of the rabbit anti-benzyl penicilloyl antibody combining sites. J Exp Med 117 161... 

As mentioned above penicillamine may split the disulphide bonds of IgM vitro, but in vivo the concentration of the thiol is far too low. Disappearance of rheumatoid factor after successful treatment is probably due to effects at the cellular level. 

E. Jellum and S. Skrede, Biological aspects of thiol-disulphide reactions during treatment with penicillamine, iji "Penicillamine research in rheumatic disease", E. Munthe, ed., Fabritius/MSD, Oslo, (1977) p. 68. 

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