Table II.
Parameter Estimates and Standard Errors from the Final LY2189102 Pharmacokinetic Model.
| Parameter | Final parameter estimate | Magnitude of inter-individual variability (%CV) | ||
|---|---|---|---|---|
| Typical value | %RSE | Final estimate | %RSE | |
| CL, L/da | 0.222 | 3.8 | 40.9 | 11.6 |
| Slope of CrCL effect, (L/d)/(mL/min) | 0.0011 | 33.0 | NE | NE |
| Shift due to ADA-positive status (%) | 37.6 | 32.2 | NE | NE |
| Vc, L | 3.08 | 7.0 | 53.9 | 20.0 |
| Q, L/d | 0.518 | 18.3 | NE | NE |
| Vp, L | 1.94 | 8.4 | 63.6 | 30.9 |
| α | 218 | 10.2 | NE | NE |
| FA b | −0.275 | 41.5 | NE | NE |
| FS b | 0.736 | 20.9 | NE | NE |
| Tka, hc | NE | NE | 50.6 | 24.5 |
| Study BBDE RV (log unit) | 0.457d | 28.9 | NA | NA |
| Study BBDK RV (log unit) | 0.263d | 14.4 | NA | NA |
| Covariance (IIV in Vc, IIV in CL) | 0.160 | 21.1 | NA | NA |
| Covariance (IIV in CL, IIV in Tka) | 0.0488 | 55.9 | NA | NA |
Minimum value of the objective function =−1222.185
α correlation factor between extent of bioavailability and half-life of absorption; CL elimination clearance; cov covariance; %CV percent coefficient of variation; F A asymptote of the hyperbolic function of dose; F S slope of the hyperbolic function of dose; IIV interindividual variability; NA not applicable; NE not estimated; Q distribution clearance; RV residual variability; SD standard deviation; %RSE percent relative standard error of the estimate; T ka half-life of absorption; V c central volume of distribution; V p peripheral volume of distribution
aThe typical value of CL is given for an ADA-negative patient with a creatinine clearance of 83.2 mL/min
bThe extent of bioavailability, F, after subcutaneous dosing is modeled with the following function of the dose, F = 1/(1 + exp(−(FA + FS/Dose)))
cThe value of Tka was computed as α × F and was modeled with inter-individual variability
dThe estimates for RV parameters are reported as variance