Table 2.
Pharmacokinetic parameters: fixed- and random-effect variabilities for FOCEI-Priors population estimation approaches
| Parameters | Unit | Definition | Published | FOCEI-Priors | ||
|---|---|---|---|---|---|---|
| Estimate | RSE% [Shrinkage] |
|||||
| Fixed-effect parameters | ||||||
| CL h_gelding | L/h | Hepatic clearance in 500-kg geldings and females | 236.8 | 242.8 | 0.2% | |
| CL h_female | L/h | 297 | 0.2% | |||
| CL r | L/h | Renal clearance in 500-kg horses | 2.845 | 3.430 | 0.7% | |
| θ BW_CL | - | Power exponent of body weight effect on clearances | - | 0.75 | FIX | |
| B max_l | ng/mL | Drug binding capacity in liver | 140.1 | 121 | 8.8% | |
| K d_l | ng/mL | Equilibrium dissociation constant in liver | 0.269 | 0.387 | 8.3% | |
| K p_r | - | Tissue-to-plasma partition coefficient in remainder | 1.09 | 1.04 | 1.9% | |
| R b | - | Blood-to-plasma ratio | 0.69 (FIX) | 0.852 | 1.3% | |
| k f, b_ISO | h− 1 |
The rate constant for DEX conversion from DEX_ISO Bioavailability of DEX_ISO in blood |
20.59 | 22.8 | 16.8% | |
| F f, b_ISO | % | 69.5% | 81.2% | 10.3% | ||
| k f, b_PHO | h− 1 |
The rate constant of DEX conversion from DEX_PHO Bioavailability of DEX_PHO in blood |
16.67 | 16.7 | FIX | |
| F f, b_PHO | % | 100% (FIX) | 100% | FIX | ||
| k f, j_PHO | h− 1 | Prodrug conversion rate constant of DEX_PHO in joints | 30 (FIX) | 30 | FIX | |
| k a, m_ISO | h− 1 |
IM absorption rate constant of DEX_ISO IM absorption rate constant of DEX |
0.0105 | 0.0115 | 2.2% | |
| k a, m_DEX | h− 1 | 0.131 | 0.131 | 19% | ||
| k a, j_DEX | h− 1 |
Rate constant for DEX absorption in joints Bioavailability of DEX in joints |
5.13 | 4.94 | 6.9% | |
| F j_DEX | % | 100 (FIX) | 100 | FIX | ||
| Between-subject variability (BSV) | ||||||
| ω 2 CLh | - | BSV in CLh | 0.094 | 15.3% [13%] | ||
| Residual unexplained variability | ||||||
| Proportional error for plasma concentration | 0.45 | 2.2% [1.2%] | ||||
| Proportional error for urine concentration | 5.44 | 8.9% [0.1%] | ||||