The pharmacokinetics of albumin conjugates of D-penicillamine in rats.
A protein conjugate that forms during the metabolism of D-penicillamine (D-PEN) in rats is electrophoretically indistinguishable from the (D-PEN-albumin) mixed disulfide that forms during the oxidation of D-PEN in plasma in vitro. Both the conjugate formed in vivo and the mixed disulfide synthesized in vitro are eliminated slowly in rats, with half-lives of 5.33 +/- 0.25 days and 3.48 +/- 0.42 days, respectively. These half-lives approximate or exceed the half-lives of radioiodinated plasma protein in the animals. The stability of the D-PEN-albumin conjugate contrasts with the rapid elimination of D-PEN itself and probably explains delayed elimination of D-PEN-containing disulfides in humans. Stable modification of tissue proteins by D-PEN may also be involved in the mode of action of D-PEN in rheumatoid arthritis.
Joyce
D A
DA
School of Physiology and Pharmacology, University of New South Wales, Department of Clinical Pharmacology and Toxicology, St. Vincent's Hospital.
Wade
D N
DN
Swanson
B R
BR
D000418:Albumins / Q000378:metabolism*; D000818:Animals; D010396:Penicillamine / Q000097:blood / Q000378:metabolism*; D011485:Protein Binding; D051381:Rats; D013997:Time Factors
D000418:Albumins; D010396:Penicillamine