D-penicillamine metabolism: the role of transformation in blood plasma.
The transformation of D-penicillamine (D-pen) was studied in orally- and intravenously-dosed rats and in human plasma in vitro. In each case, low molecular weight (LMW) metabolites (previously identified as disulphides) and a mixed disulphide between D-pen and albumin (D-pen-protein) formed. The rates of D-pen elimination, other than through protein conjugation, were comparable in the rat groups to the rate of oxidation to LMW metabolites in vitro. The rates of transformation to D-pen-protein were also comparable in the in vitro preparations and in orally-treated rats. These qualitative and quantitative similarities suggest blood plasma may be an important site of transformation in vivo. Extracellular oxidation of D-pen may be linked to its antirheumatic action, either through reduction of oxygen species or through formation of D-pen-protein disulphides at surfaces of mononuclear leukocytes.
Joyce
D A
DA
Department of Clinical Pharmacology and Toxicology, St. Vincent's Hospital, Darlinghurst, New South Wales, Australia.
Murphy
B R
BR
D000284:Administration, Oral; D000818:Animals; D001711:Biotransformation; D004220:Disulfides / Q000097:blood; D006801:Humans; D007275:Injections, Intravenous; D007700:Kinetics; D008297:Male; D008970:Molecular Weight; D010396:Penicillamine / Q000008:administration & dosage / Q000097:blood* / Q000493:pharmacokinetics; D051381:Rats; D011919:Rats, Inbred Strains; D012709:Serum Albumin / Q000378:metabolism
D004220:Disulfides; D012709:Serum Albumin; D010396:Penicillamine