Table 1 Median parameter values from final model (a) and individual animal NMR half-life and average bioavailability (b).

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

(a)

PK parameter

Median

CV%

Variance

Shrink%^

Ka (hr-1)

0.51

47.17

0.1

2.37

CL (L/hr)

0.23

49.98

0.02

0.58

K23 (hr-1)

0.05

105.93

0.05

1.13

$K30 (hr-1)

0.24

43.73

0.01

11.96

Vc (L)

1.05

41.12

0.15

0.78

Vcsf (L)

3.46

63.98

6.49

5.56

(b)

Rat

Half-life (h)

Average relative bioavailability (F)*

Average Tmax (h)

 

1

1.87

0.58

2.17

 

2

3.86

0.58

3.63

 

3

2.46

0.46

2.25

 

4

1.32

0.55

1.56

 

5

3.23

0.54

1.22

 

6

1.46

0.48

1.65

 

7**

3.23

0.58

1.19

 

8

2.80

0.32

1.7

 

9

0.98

0.62

1.15

 

10

2.65

0.41

1.9

 

Median (IQR)

2.55 (1.43–3.23)

(0.45–0.58)

1.675 (1.21–2.19)

 

Mean (SD)#

  

1.84 (0.73)

 
  1. PK pharmacokinetic, CV% coefficient of variation percent, CL NMR clearance, Vc volume central compartment, Vcsf volume cerebrospinal fluid compartment, K23 rate constant to cerebrospinal fluid from central compartment, K30 elimination rate constant from CSF compartment, IQR interquartile range, Tmax time at which Cmax was first observed.
  2. *Bioavailability was estimated after each dose given the variability of oral absorption, as described in Methods.
  3. **Rat 7 only completed 1 day of treatment.
  4. #Calculated to compare to literature values.
  5. ^Estimation to assess if the data are insufficient to precisely estimate the individual parameters.
  6. $Estimation denotes overall elimination of NMR from the CSF, including uptake by various types of cells in the CNS.
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