Pharmacokinetics and pharmacodynamics in hemophilia B dog and mini-pig. A tolerized HB dog received successive infusions of 0.4 mg/kg rFIX (100 IU/kg) and N9-GP (76 IU/kg) separated by a washout period. Blood samples were collected at indicated time points to measure (A) FIX clot activity (closed symbols) and Ag levels (open symbols) and to evaluate the ex vivo hemostatic potential by (B) WBCT and (C-D) TEG. The standard WBCT range in nonhemophilic dogs is indicated. For the TEG experiments, coagulation was triggered with kaolin. (C) Representative TEG traces recorded pre-dose (gray), at 5 minutes and 3, 19, 26, 31, 40, and 43 days (from left to right in black) after administration of N9-GP. (D) MTG values at indicated time points after administration. (E) Plasma concentrations of rFIX and N9-GP in mini-pig (3 per group) shown as individual Ag measurements after administration of 0.2 mg/kg (50 and 38 IU/kg, respectively). Solid lines represent best fits to a 2-compartment model. (F) Fitted parameters were used to simulate pharmacokinetic profiles in a multiple dose setting. Simulations were performed with N9-GP (black line) dosed every 7 (solid) or 14 (stippled) days and rFIX (gray line) dosed every 2.5 days, all at 0.2 mg/kg. Horizontal stippled lines represent 100% (top) and 1% (bottom) levels, respectively.