Pharmacokinetics of recombinant human lipocalin-type prostaglandin D synthase/beta-trace in canine.
Lipocalin-type prostaglandin (PG) D synthase (L-PGDS) is identical to beta-trace, a major protein in human cerebrospinal fluid (CSF), and acts as both a PGD(2)-producing enzyme and as an extracellular transporter for lipophilic ligands. In this study, we investigated the pharmacokinetics of recombinant human L-PGDS (rh-L-PGDS) in canines. After an intravenous bolus injection of rh-L-PGDS, the serum concentration decreased bi-exponentially with a half-life of the terminal line phase of 0.77h, which was markedly shorter than that of other proteins with the same molecular weight as that of rh-L-PGDS. The distribution volume was 55.4ml/kg, which was close to the volume of canine circulation plasma, indicating that the administrated rh-L-PGDS was distributed mainly in the blood. Only 10.3% of the administered rh-L-PGDS was excreted to the urine, suggesting that rh-L-PGDS was actively degraded within the body. After an intrathecal injection, the peak serum concentration of rh-L-PGDS was observed at 4-5h. The area under the plasma concentration-time curve obtained for 12h after the intrathecal injection was one third of the value for 3h after the intravenous injection, suggesting that at least one third of the intrathecally injected rh-L-PGDS shifted to the blood.
Li
Weidong
W
Department of Molecular Behavioral Biology, Osaka Bioscience Institute, Suita, Osaka 565-0874, Japan.
Mase
Mitsuhito
M
Inui
Takashi
T
Shimoda
Minoru
M
Isomura
Kenichi
K
Oda
Hiroshi
H
Yamada
Kazuo
K
Urade
Yoshihiro
Y
D000818:Animals; D004285:Dogs; D005260:Female; D006207:Half-Life; D006801:Humans; D007273:Injections, Intramuscular; D019746:Intramolecular Oxidoreductases / Q000097:blood / Q000134:cerebrospinal fluid / Q000493:pharmacokinetics* / Q000652:urine; D054834:Lipocalins / Q000097:blood / Q000134:cerebrospinal fluid / Q000493:pharmacokinetics* / Q000652:urine; D011994:Recombinant Proteins / Q000097:blood / Q000134:cerebrospinal fluid / Q000493:pharmacokinetics* / Q000652:urine; D013997:Time Factors
D054834:Lipocalins; D011994:Recombinant Proteins; D019746:Intramolecular Oxidoreductases; C022466:prostaglandin R2 D-isomerase