Table 3.
Descriptive summary of plasma lorlatinib and PF-06895751 pharmacokinetic parameters by renal function group
| Parameter (unit) | Normal function (n = 8) | Mild impairment (n = 8) | Moderate impairment (n = 8) | Severe impairment (n = 5) |
|---|---|---|---|---|
| Lorlatinib | ||||
| n, n2 | 8, 8 | 8, 8 | 8, 8 | 5, 5 |
| AUCinf (ng·h/mL) | 8329 (33) | 8683 (29) | 9890 (27) | 11760 (37) |
| AUClast (ng·h/mL) | 8015 (32) | 8307 (28) | 8867 (24) | 10310 (36) |
| CL/F (L/h) | 12.02 (33) | 11.51 (29) | 10.11 (27) | 8.507 (37) |
| Cmax (ng/mL) | 546.8 (48) | 549.7 (52) | 485.9 (24) | 504.8 (50) |
| t1/2 (h) | 25.64 ± 4.7500 | 28.08 ± 3.5156 | 39.40 ± 7.1019 | 41.66 ± 7.6081 |
| Tmax (h) | 1.50 (1.00–4.00) | 1.00 (1.00–1.50) | 1.25 (1.00–4.00) | 1.00 (1.00–1.50) |
| Vz/F (L) | 436.9 (24) | 462.9 (27) | 566.2 (21) | 503.8 (36) |
| PF-06895751 | ||||
| n, n2 | 8, 8 | 8, 7 | 8, 0 | 5, 0 |
| AUCinf (ng·h/mL) | 5482 (19) | 6462 (17) | NE | NE |
| AUClast (ng ·h/mL) | 4438 (18) | 5354 (19) | 5973 (28) | 4828 (58) |
| Cmax (ng/mL) | 56.35 (27) | 65.99 (26) | 63.65 (28) | 52.82 (59) |
| t1/2 (h) | 40.66 ± 11.671 | 35.46 ± 5.5907 | NE | NE |
| Tmax (h) | 24.0 (12.0–48.0) | 24.0 (12.0–72.0) | 72.0 (48.0–120) | 72.0 (72.0–96.0) |
| MRAUCinf | 1.453 (21) | 1.701 (36) | NE | NE |
| MRAUClast | 1.223 (29) | 1.421 (39) | 1.487 (44) | 1.034 (66) |
| MRCmax | 0.2274 (44) | 0.2650 (57) | 0.2890 (22) | 0.2310 (74) |
Geometric mean (geometric % coefficient of variation) values are shown for all data except that the median (range) is reported for Tmax and the arithmetic mean ± standard deviation for t1/2
AUCinf area under the plasma concentration–time profile (AUC) from time 0 extrapolated to infinity, AUClast AUC from time 0 to last quantifiable concentration, CL/F apparent oral clearance, Cmax maximum observed plasma concentration, MRAUCinf metabolite to parent ratio for AUCinf, MRAUClast metabolite to parent ratio for AUClast, MRCmax metabolite to parent ratio for Cmax, t1/2 terminal elimination half-life, Tmax time to Cmax, Vz/F apparent volume of distribution, n number of participants contributing to the summary statistics, n2 number of participants contributing to the summary statistics for AUCinf, MRAUCinf, and t1/2, NE not estimable