Table 3. Spinal Cord Pharmacokinetic Parameters of Complement C5a Receptor 1 Antagonistsa.
| PMX53 | PMX205 | ||||||||
|---|---|---|---|---|---|---|---|---|---|
| parameters | units | i.v. | s.c. | i.p. | p.o. | i.v. | s.c. | i.p. | p.o. |
| Cmax | ng/g | 129.82 | 96.56 | 71.26 | 75.88 | 449.84 | 225.14 | 219.65 | 214.33 |
| Tmax | min | 23.15 | 11.86 | 14.89 | 45.90 | 17.48 | 63.47 | ||
| Vss | μg/(ng/g) | 0.33 | 0.27 | ||||||
| V1_F | μg/(ng/g) | 0.23 | 0.12 | 0.35 | 0.32 | 0.07 | 0.05 | 0.06 | 0.05 |
| CL_F | ng/(min ng/g) | 1.52 | 3.68 | 5.15 | 2.33 | 1.63 | 1.00 | 0.99 | 0.81 |
| V2_F | μg/(ng/g) | 0.10 | 0.26 | <0.01 | 0.16 | 0.20 | 0.05 | 0.14 | <0.001 |
| CLD2_F | ng/(min ng/g) | 30.58 | 1.36 | 0.01 | 2.71 | 21.89 | 0.07 | 2.59 | <0.001 |
| K01 | 1/hr | 2.70 | 15.39 | 11.20 | 1.34 | 4.45 | 0.99 | ||
| K10 | 1/hr | 0.40 | 1.87 | 0.87 | 0.44 | 1.46 | 1.25 | 1.05 | 0.90 |
| K12 | 1/hr | 7.94 | 0.69 | <0.01 | 0.51 | 19.69 | 0.08 | 2.75 | <0.01 |
| K21 | 1/hr | 18.30 | 0.32 | 0.19 | 1.00 | 6.59 | 0.32 | 1.08 | 0.33 |
| K01_HL | min | 15.39 | 2.70 | 3.71 | 30.93 | 9.36 | 42.04 | ||
| K10_HL | min | 105.04 | 22.22 | 47.70 | 94.33 | 28.39 | 34.79 | 39.53 | 46.04 |
| Alpha | 1/hr | 26.36 | 2.66 | 0.87 | 1.69 | 27.40 | 1.28 | 4.64 | 0.90 |
| Beta | 1/hr | 0.27 | 0.22 | 0.19 | 0.26 | 0.35 | 0.32 | 0.24 | 0.33 |
| Alpha_HL | hr | 0.03 | 0.26 | 0.79 | 0.41 | 0.03 | 0.55 | 0.15 | 0.77 |
| Beta_HL | hr | 2.52 | 3.09 | 3.71 | 2.66 | 1.97 | 2.16 | 2.84 | 2.08 |
| MRT_last | hr | 0.69 | 0.64 | 0.62 | 0.68 | 0.62 | 0.81 | 0.65 | 0.80 |
| MRT_INF_obs | hr | 4.86 | 1.49 | 1.16 | 1.89 | 2.45 | 2.71 | 1.34 | 1.06 |
| MRT_INF_pred | hr | 4.86 | 1.46 | 1.13 | 1.88 | 2.45 | 2.69 | 1.31 | 1.07 |
Cmax: peak drug concentration; Tmax: time to reach peak concentration following drug administration; Vss: apparent volume of distribution at a steady state; V1_F and V2_F: apparent volume of central and peripheral compartment in two compartmental models; CL_F and CLD2_F: apparent total body clearance of the drug and apparent total clearance of the drug after administration; K01: absorption rate constant; K10: elimination rate constant; K12 and K21: distribution and redistribution rate constant; K01_HL and K10_HL: distribution half-life and elimination half-life; Alpha and Beta: hybrid first-order rate constants expressing initial and terminal slopes of distribution and elimination phases; Alpha_HL and Beta_HL: initial or disposition half-life and terminal elimination half-life; MRT_last, MRT_INF_obs, and MRT_INF-pred: mean residence time at the last time point, infinity observed, and infinity predicted using two-compartmental analysis.