Table 3.
(A) Descriptive and (B) Statistical Summaries of Plasma M1 (PF‐06471658), M2 (PF‐07055087), and M4 (PF‐07054874) Pharmacokinetic Parameters in Subjects With Normal Renal Function or Renal Impairment Following a Single 200‐mg Oral Dose of Abrocitinib
| (A) Pharmacokinetic Parameter Summary | |||
|---|---|---|---|
| Parameter, Unita | Normal Renal Function, N = 8 | Moderate Renal Impairment, N = 7 | Severe Renal Impairment, N = 8 |
| AUCinf, ng • h/mL | |||
| M1 | 872.6 (44) | 1346 (43) | 2505 (45) |
| M2 | 1476 (31) | 3981 (38) | 8433 (25) |
| M4 | 2450 (41) | 7543 (30) | 13280 (44) |
| AUClast, ng • h/mL | |||
| M1 | 854.7 (45) | 1330 (44) | 2481 (47) |
| M2 | 1394 (32) | 3894 (39) | 8115 (23) |
| M4 | 2420 (42) | 7474 (30) | 12700 (44) |
| Cmax, ng/mL | |||
| M1 | 193.7 (54) | 192.8 (65) | 325.0 (81) |
| M2 | 241.3 (34) | 331.6 (21) | 429.3 (28) |
| M4 | 427.4 (37) | 671.5 (19) | 616.7 (40) |
| tmax, h | |||
| M1 | 1.00 (0.50‐3.00) | 2.00 (1.00‐3.00) | 1.50 (1.00‐6.00) |
| M2 | 2.00 (1.00‐3.00) | 4.00 (2.00‐6.00) | 4.00 (2.00‐8.00) |
| M4 | 1.50 (0.50‐3.00) | 4.00 (2.00‐6.00) | 3.50 (2.00‐8.00) |
| t1/2, h | |||
| M1 | 4.7 ± 2.3 | 5.9 ± 2.4 | 6.4 ± 2.9 |
| M2 | 4.9 ± 3.0 | 6.7 ± 1.2 | 13.0 ± 5.1 |
| M4 | 7.9 ± 6.2 | 12.5 ± 8.1 | 15.6 ± 4.4 |
| MRAUCinf | |||
| M1 | 0.17 (101) | 0.15 (77) | 0.39 (138)b |
| M2 | 0.29 (63) | 0.43 (45) | 1.32 (72)b |
| M4 | 0.48 (35) | 0.82 (36) | 2.19 (40)b |
| Adjusted (Least‐Squares) Geometric Means | ||||
|---|---|---|---|---|
| (B) Statistical Comparison | Test | Reference | Ratio (Test/Reference) of Adjusted Geometric Meansc | 90% CI for Ratioc |
| Moderate Renal Impairment (Test) Versus Normal Renal Function (Reference) | ||||
| AUCinf, ng • h/mL | ||||
| M1 | 1345.8 | 872.7 | 154.22 | (105.11‐226.26) |
| M2 | 3981.2 | 1475.7 | 269.78 | (196.61‐370.18) |
| M4 | 7543.0 | 2449.9 | 307.89 | (224.18‐422.86) |
| AUClast, ng • h/mL | ||||
| M1 | 1329.6 | 854.7 | 155.56 | (105.45‐229.49) |
| M2 | 3893.6 | 1393.8 | 279.36 | (202.56‐385.29) |
| M4 | 7474.0 | 2420.1 | 308.83 | (223.94‐425.91) |
| Cmax, ng/mL | ||||
| M1 | 192.8 | 193.7 | 99.51 | (59.80‐165.57) |
| M2 | 331.6 | 241.3 | 137.43 | (106.82‐176.81) |
| M4 | 671.5 | 427.4 | 157.13 | (120.95‐204.13) |
| Severe Renal Impairment (Test) Versus Normal Renal Function (Reference) | ||||
| AUCinf, ng • h/mL | ||||
| M1 | 2505.0 | 872.7 | 287.06 | (196.72‐418.89) |
| M2 | 8432.5 | 1475.7 | 571.43 | (447.27‐730.05) |
| M4 | 13278.7 | 2449.9 | 542.01 | (378.71‐775.73) |
| AUClast, ng • h/mL | ||||
| M1 | 2481.3 | 854.7 | 290.30 | (197.65‐426.38) |
| M2 | 8114.5 | 1393.8 | 582.21 | (455.77‐743.73) |
| M4 | 12702.5 | 2420.1 | 524.88 | (365.23‐754.31) |
| Cmax, ng/mL | ||||
| M1 | 325.0 | 193.7 | 167.79 | (97.20‐289.64) |
| M2 | 429.3 | 241.3 | 177.92 | (135.91‐232.92) |
| M4 | 616.7 | 427.4 | 144.29 | (104.21‐199.80) |
AUCinf, area under the concentration‐time curve (AUC) from time 0 extrapolated to infinite time; AUClast, AUC from time 0 to time of last quantifiable concentration; Cmax, maximum plasma concentration; CI, confidence interval; MRAUCinf, metabolite/abrocitinib ratio based on AUCinf; t1/2, terminal elimination half‐life; tmax, time to Cmax.
N = total number of subjects in the treatment group.
aGeometric mean (geometric % coefficient of variation) for all except median (range) for tmax and arithmetic mean ± standard deviation for t1/2.
bN = 7.
cThe ratios (and 90% CI) are expressed as percentages.