Pharmacokinetics of recombinant human lipocalin-type prostaglandin D synthase/β-trace in canine

Lipocalin-type prostaglandin (PG) D synthase (L-PGDS) is identical to β-trace, a major protein in human cerebrospinal fluid (CSF), and acts as both a PGD2-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 0.77 h, which was markedly shorter than that of other proteins with the same molecular weight as that of rh-L-PGDS. The distribution volume was 55.4 ml/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 4-5 h. The area under the plasma concentration-time curve obtained for 12 h after the intrathecal injection was one third of the value for 3 h after the intravenous injection, suggesting that at least one third of the intrathecally injected rh-L-PGDS shifted to the blood.