Characterization of C-terminal-truncated urinary metabolites of a recombinant hirudin in rats.
Although it has been reported that hirudin was excreted in urine mainly as its nonmetabolized form in humans, dogs, and rabbits, no report has been published about the molecular nature of urinary metabolites in rats. We found that nonmetabolized hirudin could not be detected in rat urine after its i.v. administration and that urinary metabolites of recombinant hirudin CX-397 consisted of at least the following six C-terminal-truncated peptides: CX-397(1-49), CX-397(1-50), CX-397(1-51), CX-397(1-52), CX-397(1-54), and CX-397(1-55), in the ratio of roughly 11, 51, 3, 11, 19, and 5%, respectively. In conclusion, the urinary metabolism of recombinant hirudin in rats is different from that in humans, dogs, and rabbits, suggesting that the handling of hirudin in rat kidney is unique among them.
Komatsu
Y
Y
Pharmaceuticals and Biotechnology Laboratory, Japan Energy Corporation, Saitama, Japan. ykomatsu@j-energy.co.jp
Hayashi
H
H
D000595:Amino Acid Sequence; D000596:Amino Acids / Q000032:analysis; D000818:Animals; D002850:Chromatography, Gel; D002851:Chromatography, High Pressure Liquid; D004285:Dogs; D006629:Hirudins / Q000031:analogs & derivatives* / Q000737:chemistry / Q000378:metabolism / Q000652:urine; D006801:Humans; D008297:Male; D008969:Molecular Sequence Data; D010446:Peptide Fragments / Q000737:chemistry / Q000378:metabolism / Q000652:urine; D011817:Rabbits; D051381:Rats; D017207:Rats, Sprague-Dawley; D011994:Recombinant Proteins / Q000737:chemistry / Q000378:metabolism / Q000652:urine; D013045:Species Specificity
D000596:Amino Acids; C100322:CX 397; D006629:Hirudins; D010446:Peptide Fragments; D011994:Recombinant Proteins