Table 2. Brain 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 | 74.13 | 120.37 | 48.08 | 76.99 | 76.99 | 161.76 | 155.70 | 153.70 |
| Tmax | min | 19.87 | 10.45 | 14.89 | 30.23 | 19.85 | 20.71 | ||
| Vss | μg/(ng/g) | 0.74 | 0.54 | ||||||
| V1_F | μg/(ng/g) | 0.40 | 0.15 | 0.31 | 0.31 | 0.13 | 0.08 | 0.08 | 0.18 |
| CL_F | ng/(min ng/g) | 2.43 | 1.75 | 3.77 | 2.28 | 2.56 | 1.66 | 1.27 | 0.75 |
| V2_F | μg/(ng/g) | 0.33 | 0.08 | 0.40 | 0.16 | 0.41 | 0.07 | 0.19 | <0.001 |
| CLD2_F | ng/(min ng/g) | 107.59 | 2.91 | 25.61 | 2.68 | 43.73 | 0.70 | 2.71 | <0.001 |
| K01 | 1/h | 5.81 | 9.06 | 11.20 | 2.35 | 3.81 | 11.27 | ||
| K10 | 1/h | 0.36 | 0.68 | 0.72 | 0.44 | 1.16 | 1.26 | 0.90 | 0.25 |
| K12 | 1/h | 15.95 | 1.13 | 4.92 | 0.51 | 19.79 | 0.53 | 1.92 | <0.001 |
| K21 | 1/h | 19.41 | 2.07 | 3.87 | 0.99 | 6.40 | 0.61 | 0.87 | 2.88 |
| K01_HL | min | 7.16 | 4.59 | 3.71 | 17.71 | 10.91 | 3.69 | ||
| K10_HL | min | 115.54 | 60.95 | 57.39 | 94.86 | 35.89 | 32.91 | 46.56 | 165.07 |
| Alpha | 1/h | 35.52 | 3.48 | 9.22 | 1.68 | 27.08 | 2.03 | 3.45 | 2.88 |
| Beta | 1/h | 0.20 | 0.41 | 0.30 | 0.26 | 0.27 | 0.38 | 0.23 | 0.25 |
| Alpha_HL | h | 0.02 | 0.20 | 0.08 | 0.41 | 0.03 | 0.34 | 0.20 | 0.24 |
| Beta_HL | h | 3.52 | 1.71 | 2.28 | 2.69 | 2.53 | 1.83 | 3.08 | 2.75 |
| MRT_last | h | 0.70 | 0.70 | 0.68 | 0.68 | 0.64 | 0.72 | 0.66 | 0.75 |
| MRT_INF_obs | h | 5.46 | 1.98 | 2.29 | 1.89 | 3.88 | 1.85 | 1.24 | 2.43 |
| MRT_INF_pred | h | 5.45 | 1.97 | 2.30 | 1.88 | 3.88 | 1.82 | 1.24 | 2.44 |
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 compartments 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.