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. 2024 Apr 30;67(16):13550–13571. doi: 10.1021/acs.jmedchem.3c02469

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)
a

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.

b

Suspension in 2% (v/v) Tween 80 in of 0.5% (w/v) methylcellulose in water.

c

Suspension in 1% (v/v) Soluplus and 0.5% (w/v) methylcellulose in water.

d

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.

e

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.

f

AUC0-∞.