Clearance extensive metabolizers (L/h)b
|
24.3 (20.5,
29.3) |
BSV: 23.1 (15.2, 32.9) |
Clearance poor metabolizers (L/h)b
|
7.87 (6.04, 9.75) |
BSV: 23.1 (15.2, 32.9) |
Central volume of distribution (L)b
|
14.4 (8.70,
20.3) |
|
Intercompartmental clearance (L/h)b
|
6.47 (2.80,
11.3) |
|
Peripheral volume of distribution (L)b
|
7.71 (5.78,
10.5) |
|
Relative bioavailability () |
1 Fixed |
BOV: 23.1 (15.2,
29.9) |
Absorption rate constant (1/h) |
4.80 (2.89, 6.39) |
BOV: 485 (211,
916) |
Mean transit time (h) |
1.75 (1.54, 1.94) |
BOV: 38.8 (29.1,
48.5) |
Number of transit compartments |
10 Fixedd
|
|
Covariatese |
Covariatese |
Covariatese |
Change in clearance on day five for non-pregnant extensive metabolizers
(%)*
|
-54.9 (-63.5, -48.2) |
|
Change in bioavailability on day five for non-pregnant
(%)*
|
+33.0 (10.0, 52.0) |
|
Change in clearance on day one for pregnant (%)*
|
-42.2 (-61.6, -14.9) |
|
Change in mean transit time for PIE (%)*
|
-71.9
(-79.3, -58.2) |
|
Change in mean transit time for Hunfeld et al.
(%)*
|
-43.1 (-68.7, -30.0) |
|
Residual unexplained variability |
Residual unexplained
variability |
Residual unexplained variability |
Proportional error (%) |
36.7 (32.7, 40.5) |
|
Additive error (mg/L) |
20% of LLOQf
|
|
a95% confidence intervals obtained by non-parametric
bootstrap (n=500)
bAllometric scaling with total body weight for a
reference individual of 70 kg
cBetween-subject (BSV) and between-occasion
variability (BOV) were obtained using the formula
\(\text{sqrt}(\exp\left(OM^{2}\right)-1)\) and reported as
approximate %CV
dThe number of transit compartments was fixed to 10 to
make parameter estimates more stable
eStudy effect was tested on parameters with day one
data from healthy, non-pregnant participants as reference group
*Reference group is day one non-pregnant (non-pregnant
group after single dose)
fLower limit of quantification (LLOQ) (mg/L) was
study-specific: 0.001 for PIE, 0.0260 for Hunfeld et al., and
0.00503 for Helgadóttir et al.
|
a95% confidence intervals obtained by non-parametric
bootstrap (n=500)
bAllometric scaling with total body weight for a
reference individual of 70 kg
cBetween-subject (BSV) and between-occasion
variability (BOV) were obtained using the formula
\(\text{sqrt}(\exp\left(OM^{2}\right)-1)\) and reported as
approximate %CV
dThe number of transit compartments was fixed to 10 to
make parameter estimates more stable
eStudy effect was tested on parameters with day one
data from healthy, non-pregnant participants as reference group
*Reference group is day one non-pregnant (non-pregnant
group after single dose)
fLower limit of quantification (LLOQ) (mg/L) was
study-specific: 0.001 for PIE, 0.0260 for Hunfeld et al., and
0.00503 for Helgadóttir et al.
|
a95% confidence intervals obtained by non-parametric
bootstrap (n=500)
bAllometric scaling with total body weight for a
reference individual of 70 kg
cBetween-subject (BSV) and between-occasion
variability (BOV) were obtained using the formula
\(\text{sqrt}(\exp\left(OM^{2}\right)-1)\) and reported as
approximate %CV
dThe number of transit compartments was fixed to 10 to
make parameter estimates more stable
eStudy effect was tested on parameters with day one
data from healthy, non-pregnant participants as reference group
*Reference group is day one non-pregnant (non-pregnant
group after single dose)
fLower limit of quantification (LLOQ) (mg/L) was
study-specific: 0.001 for PIE, 0.0260 for Hunfeld et al., and
0.00503 for Helgadóttir et al.
|