PB0330 - Pharmacokinetics of protein C concentrate after subcutaneous and intravenous administration in Göttingen minipigs

Background: Protein C concentrate (human) (PC; Baxalta Inc., a Takeda company) is currently only approved for intravenous (IV) administration, although off-label subcutaneous (SC) administration has been reported in clinical practice. Data comparing the pharmacokinetics (PK) of PC between these two routes of administration are lacking.

Aims: To determine the PK profile and safety of PC when administered via IV and SC routes in Göttingen minipigs.

Methods: Göttingen minipigs (per route: male, n=3; female, n=3) received a single slow bolus dose of PC via the IV (100 IU/kg) or the SC (300 IU/kg) route. Plasma samples for PK analysis were collected pre-dose and at 0.083, 1, 4, 8, 12, 16, 24, 32, 48, 72, 96 and 120 hours post-dose. PK parameters were generated from individual plasma PC concentrations, as measured by a human PC-specific ELISA, and estimated by non-compartmental analysis. This study was funded by Baxalta Innovations GmbH, a Takeda company.

Results: Systemic exposure to PC appeared to be sex-independent following IV or SC administration. Mean absolute bioavailability of PC was 37.8% after SC administration, with a median (range) time to peak PC concentration of 8 (4–12) hours. Mean plasma half-life of PC after IV and SC administration was 21.0 hours and 21.1 hours, respectively. Following IV administration, mean total body clearance (Cl) of PC was 7.54 mL/h/kg and mean volume of distribution based on the terminal elimination phase (Vz) was 224 mL/kg. For SC administration, mean values for Cl and Vz (divided by the fraction of dose absorbed) were 18.9 mL/h/kg and 568 mL/kg, respectively. No PC-related adverse effects or histopathological findings were observed following IV or SC administration.

Conclusion(s): The PK profile of PC was well characterized following IV and SC administration. Bioavailability of SC PC was approximately 40%. PC was well tolerated after IV and SC administration.