Table 5. Comparison of Single High-Dose p.o. Pharmacokinetics of 9 and Nirmatrelvir (1) in Ratsa.
Compd | Dose (mg/kg) | Form | Cmax (ng/mL) | Tmax (h) | AUC0–24 (ng·h/mL) |
---|---|---|---|---|---|
9 | 100 | Crystallineb | 7210 ± 2880 | 0.5 ± 0 | 15000 ± 1310 |
75% SDDc | 2830 ± 1150 | 1 ± 0 | 13400 ± 2950 | ||
1000 | Crystallineb | 52700 ± 7990 | 2.8 ± 2 | 500000 ± 211000 | |
75% SDDc | 59200 ± 16600 | 2.7 ± 1.2 | 565000 ± 124000 | ||
Nirmatrelvir (1) | 10 | Crystalline Anhydrous Form 1d | 1450 ± 373 | 0.25 ± 0 | 2170 ± 1180f |
100 | Crystalline Anhydrous Form 1b | 5300 ± 1380 | 1.4 ± 1.0 | 18000 ± 8880 | |
10 | MTBEe | 1290 (851, 1730) | 1.5 (1.0, 2.0) | 3190 (1890, 4480) | |
100 | MTBEb | 29100 (32400, 25800) | 0.75 (1.0, 0.5) | 68300 (78200, 58400) | |
1000 | MTBEb | 88300 (75500, 101000) | 1.0 (1.0, 1.0) | 746500 (795000, 698000) |
Pharmacokinetic parameters for 9 and 1 were generated from plasma-concentration time data and are reported as mean ± S.D. (n = 3) or mean and individual values (n = 2). Pharmacokinetic studies were performed in male Wistar–Han rats in the fed state.
Suspension in 2% (v/v) Tween 80 in of 0.5% (w/v) methylcellulose in water.
Suspension in 1% (v/v) Soluplus and 0.5% (w/v) methylcellulose in water.
Crystalline anhydrous form 1 of 1 administered as a solution in 2% (v/v) Tween 80/98% 0.5% (w/v) methyl cellulose in water.
Crystalline MTBE cosolvate of 1 administered as a solution in 10% (v/v) ethanol/10% (v/v) Capmul MCM/35% (v/v) PEG400/45% (v/v) Tween 80.
AUC0-∞.