Table 4.
Summary of pharmacokinetic parameters of MK-8242 following 30 – 250 mg doses of MK-8242 administered once-daily (QD) or twice-daily (BID) on Days 1 and 7 (only 1 dose was administered on Day 7 in BID panels to support PK characterization). PK parameters are maximum concentration (Cmax), time of maximum concentration (Tmax), area under the concentration-time curve from 0 to 12 hr (AUC0-12hr), area under the concentration-time curve from 0 to 24 hr (AUC0-24hr), terminal half-life (t1/2), apparent total body steady-state clearance (CLss/F), volume of distribution at steady-state (Vss/F). All PK parameters are geometric means (% coefficient of variation), except for Tmax, which is median (range).
| Dose | N | Day | Cmax (nM)a | Tmax (hr)b | AUC0-12hr (hr*nM)a | AUC0-24hr (hr*nM)a | t1/2 (hr)a | CLss/F (L/hr)a | Vss/F (L)a |
|---|---|---|---|---|---|---|---|---|---|
| 30 mg QD | 1 | 1 | 56.7 | 6.2 | 398 | 604 | -- | -- | -- |
| 1 | 7 | 88.8 | 2.0 | 522 | 665 | 4.7 | 53.7 | 364 | |
| 60 mg QD | 1 | 1 | 109 | 2.0 | 510 | 510 | -- | -- | -- |
| 1 | 7 | 178 | 2.0 | 515 | 515 | -- | 139 | -- | |
| 120 mg QD | 3 | 1 | 416 (81) | 4.0 (2.1 – 4.0) | 2780 (107) | 3710 (126) | -- | -- | -- |
| 3 | 7 | 530 (56) | 2.0 (1.0 – 2.0) | 2800 (52) | 3460 (55) | 5.33 (24) | 41.3 (55) | 318 (34) | |
| 120 mg BID | 4 | 1 | 561 (52) | 4.0 (2.1 – 4.0) | 2810 (90)c | 3230 (101)c | -- | -- | -- |
| 3 | 7 | 744 (56) | 4.0 (2.0 – 4.0) | 3360 (42) | 4180 (41) | -- | 42.5 (42) | -- | |
| 250 mg QD | 1 | 1 | 1270 | 4.0 | 7930 | 10900 | -- | -- | -- |
| 1 | 7 | 1320 | 2.0 | 6070 | 6840 | 4.57 | 43.5 | 287 | |
| 170 mg BID | 3 | 1 | 984 (93) | 2.0 (2.0 – 4.1) | 5940 (135)d | 6940 (127)d | -- | -- | -- |
| 3 | 7 | 1200 (65) | 4.2 (2.2 – 6.0) | 6220 (83) | 8440 (105) | 10.30e | 32.5 (83) | 775e | |
| 210 mg BID | 5 | 1 | 1310 (52) | 2.0 (1.9 – 4.1) | 5500 (64)f | 6400 (76)f | -- | -- | -- |
| 5 | 7 | 1550 (51) | 4.0 (2.0 – 6.0) | 8670 (48) | 11200 (53) | 7.92 (32)c | 28.8 (48) | 317 (50)c | |
| 250 mg BID | 3 | 1 | 1510 (66) | 2.0 (2.0 – 4.0) | 6710 (76) | 7910 (82) | -- | -- | -- |
| 3 | 7 | 1500 (108) | 2.0 (1.9 – 4.1) | 7240 (74) | 8800 (57) | 5.21 (18)d | 41.1 (74) | 222 (70)d | |
| 300 mg BID | 3 | 1 | 1940 (26) | 2.1 (2.0 – 6.0) | 8300e | 9480e | -- | -- | -- |
| 3 | 7 | 1920 (81) | 4.0 (4.0 – 6.0) | 10100 (50) | 14200 (62) | 7.06 (37)d | 35.4 (50) | 384 (31)d |
Geometric mean (%CV);
Median (min - max);
N=3;
N=2;
N=1;
N=4;