Table 2 NMR plasma and CSF PK exposures estimated using Bayesian posteriors for AUC0-endoftreatment and Cmax_0-5 days and percent penetration of NMR into the CSF compared to blood.

From: In-vitro and in-vivo assessment of nirmatrelvir penetration into CSF, central nervous system cells, tissues, and peripheral blood mononuclear cells

Animal

Cmax_0-5 days (ng/mL) Plasma

AUC0-endoftreatment (µg*hr/mL) Plasma

AUCdaily_average (µg*hr/mL) Plasma

Cmax_0-5 days (ng/mL) CSF

AUC0-endoftreatment (µg*hr/mL) CSF

AUCdaily_average (µg*hr/mL) CSF

% Penetration by Cmax CSF/Plasma

% Penetration by AUC CSF/Plasma

1

2270

160

32

105.81

7.11

1.42

4.66

4.44

2

3660

189

37.8

252

12.5

2.5

6.89

6.61

3

2020

92.7

18.54

655.8

28.9

5.78

32.47

31.175

4

796

76.3

15.26

144

11.6

2.32

18.10

15.20

5

1860

80.7

16.14

1169.9

52.21

10.44

62.84

64.7

6

2218

128

25.6

560

30.2

6.04

25.27

23.59

7#

4550

19.55

3.91

NA

NA

NA

NA

NA

8

3857.9

99.8

19.96

1107

28.6

5.72

28.70

28.66

9

4879.3

205

41

410

17.4

3.48

8.41

8.49

10

1862.7

128

25.6

271.6

17.6

3.52

14.58

13.75

Median (IQR)

2240 (1860–4030)

113.9 (79.6–167.3)

22.78 (15.92–33.45)

410 (200–880)

17.6 (12.05–29.55)

3.52 (2.41–5.91)

18.1 (7.65–30.59)

15.2 (7.55–29.92)

Median (IQ R)*

2220 (1860–3760)

128 (86.7–174.5)

25.6 (17.34–34.9)

–

–

–

–

–

Geometric mean*# (Geometric SD factor)

2480 (1730)

–

20.25 (1.956)

–

–

–

–

–

  1. Units for Cmax converted to ng/mL for consistency. AUC kept in µg*hr/mL.
  2. Cmax maximum concentration, AUC area under the curve, CSF cerebral spinal fluid, T ½ half = life, IQR interquartile range, SD standard deviation.
  3. *Excluding rat 7 as no CSF was obtained from this animal, #Calculated to compare to clinical data.
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