Pharmacokinetic parameters of ABT-384, A-1331480, and A-847082 following a 10-mg single dose of ABT-384 with and without ketoconazole (KTZ) coadministration in healthy adults
| Parameter | Parameter Estimate (S.E.M.%) | IIV [ω2] | IOV [ω2] | With KTZ | RV [σ2] |
|---|---|---|---|---|---|
| ABT-384 | |||||
| KTR (1/h) | 3.82 (14%) | 0.166 | 0.138 | 11% ↓ | |
| CLABT384 (l/h) | 4.25 (22%) | 0.021 | 0.060 | 69.3% ↓ | |
| Q ABT384 (l/h) | 1.41 (18%) | – | – | – | |
| Vp, ABT384 (l) | 33.2 (24%) | 0.020 | 0.038 | 91.1% ↑ | |
| Vt, ABT384 (l) | 18.5 (21%) | – | – | – | |
| F1ABT384 | 0.181 (23%) | 0.117 | – | 1 FIX | |
| aAUCABT384 (ng ⋅ h/ml) | 426 | – | – | 7664 | |
| 0.015 (Additive) | |||||
| 0.048 (Proportional) | |||||
| A1331480 | |||||
| fm1* | 0.231 (11%) | 0.0374 | – | 98% ↓ | |
| km1 | 0.843 (11%) | 0.0124 | – | 97% ↓ | |
| aAUCA1331480 (ng ⋅ h/ml) | 496 | – | – | 1963 | |
| 0.0379 (Additive) | |||||
| 0.0428 (Proportional) | |||||
| A847082 | |||||
| fm2* | 0.0011 (7.5%) | 0.0738 | – | 105% ↑ | |
| km2 | 0.0364 (20%) | 0.412 | – | 70% ↓ | |
| aAUCA847082 (ng ⋅ h/ml) | 54.6 | – | – | 2073 | |
| 0.35 (Additive) | |||||
| 0.00831 (Proportional) |
Fl, bioavailability; IIV, inter-individual variability; IOV, inter-occasion variability; KTR, first-order transition absorption rate constant; Q, distribution clearance; RV, residual variability, Vp, volume distribution of the central compartment; Vt, volume distribution of the peripheral compartment; –, not determined.
↵a AUC∞ values were calculated using eq. 1 for ABT-384, eq. 2 for A-1331480, and eq. 3 for A-847082.