Table 2.
Pharmacokinetic parameters
|
C
max
[ng/ml] |
AUC0−tz
[ng x h/ml] |
AUC0−∞
[ng x h/ml] |
t
max
a
[h] |
t
1/2
[h] |
CLb
[ml/min] |
V
z
b
[L] |
|
|---|---|---|---|---|---|---|---|
| 2 mg IV (n = 6) | |||||||
| gmean | 51.5 | 32.9 | NC | 1.00 | NC | NC | NC |
| gCV (%) | 16.9 | 19.3 | NC | 1.00–1.00 | NC | NC | NC |
| 6 mg IV (n = 6) | |||||||
| gmean | 318 | 507 | 721 | 1.00 | 3.93 | 139 | 47.2 |
| gCV (%) | 18.3 | 34.4 | 22.4 | 1.00–1.02 | 26.6 | 22.4 | 34.9 |
| 20 mg IV (n = 6) | |||||||
| gmean | 3410 | 43,100 | 44,400 | 1.38 | 15.6 | 7.50 | 10.1 |
| gCV (%) | 36.7 | 74.1 | 71.6 | 1.00–2.00 | 25.1 | 71.6 | 90.1 |
| 60 mg IV (n = 6) | |||||||
| gmean | 12,900 | 586,000 | 590,000 | 1.63 | 45.6 | 1.69 | 6.69 |
| gCV (%) | 18.4 | 38.7 | 38.5 | 1.00–3.17 | 23.6 | 38.5 | 45.4 |
| 120 mg IV (n = 6) | |||||||
| gmean | 35,800 | 2970,000 | 2,980,000 | 1.25 | 87.4 | 0.672 | 5.08 |
| gCV (%) | 14.4 | 20.0 | 20.0 | 1.00–3.00 | 22.7 | 20.0 | 15.5 |
| 40 mg SC (n = 5) | |||||||
| gmean | 122 | 18,000 | NC | 96.1 | NC | NC | NC |
| gCV (%) | 94.1 | 73.2 | NC | 72–168 | NC | NC | NC |
| 80 mg SC (n = 6) | |||||||
| gmean | 717 | 120,000 | 130,000 | 120 | 138 | 10.2 | 122 |
| gCV (%) | 151 | 134 | 119 | 96.1–120 | 25.1 | 119 | 150 |
| 120 mg SC (n = 6) | |||||||
| gmean | 4970 | 888,000 | 900,000 | 108 | 117 | 2.22 | 22.6 |
| gCV (%) | 97.9 | 144 | 143 | 95.8–120 | 101 | 143 | 83.4 |
Arithmetic means (SDs) for pharmacokinetic parameters are provided in online resource 1 Supplemental Table S2
AUC 0−∞ area under the concentration–time curve of the analyte in plasma over the time interval from 0 to extrapolated to infinity, AUC 0−tz area under the concentration–time curve of the analyte in plasma over the time interval from 0 to the last measurable time point of the dose, CL total clearance of the analyte in plasma after intravascular administration, C max maximum measured concentration of the analyte in plasma, gCV geometric coefficient of variation, gmean geometric mean, IV intravenous, NC not calculated, SC subcutaneous, t 1/2 terminal elimination half-life of the analyte in plasma, t max time from dosing to the maximum measured concentration of the analyte in plasma or the maximum measured biomarker effect, V z apparent volume of distribution during the terminal phase after an intravascular dose
aData for t max are presented as median (range)
bCL and V z expressed as functions of bioavailability (CL/F and V z/F) for SC parameters