Pharmacokinetic parameters of DPHM (or [2H10]-DPHM), preformed DPMA, and in vivo formed DPMA in pregnant sheep
| Pharmacokinetic Parameter | E1225A | E2174 | E303Y | E4227 | E4230 | Mean ± S.D. | |
|---|---|---|---|---|---|---|---|
| Maternal | |||||||
| DPHM (or [2H10]-DPHM) | CLtb(ml/min/kg) | 54.1 | 24.9 | 56.6 | 31.1 | 38.0 | 40.9 ± 14.0 |
| Vd ss(l/kg) | 3.6 | 1.1 | 2.5 | 1.0 | 2.3 | 2.1 ± 1.1 | |
| T 1/2β(min) | 49.0 | 56.5 | 33.7 | 83.1 | 63.6 | 57.2 ± 18.2 | |
| MRT (min) | 67.1 | 42.7 | 43.7 | 89.3 | 61.0 | 60.8 ± 19.1 | |
| Preformed DPMA Metabolite | CLtb(ml/min/kg) | 0.86 | 0.43 | 0.46 | 0.48 | 0.52 | 0.55 ± 0.18 |
| Vd ss(l/kg) | 0.11 | 0.08 | 0.13 | 0.09 | 0.09 | 0.10 ± 0.02 | |
| T 1/2β(min) | 102.9 | 138.0 | 339.9 | 150.4 | 143.4 | 174.9 ± 94.0 | |
| MRT (min) | 130.1 | 187.4 | 282.7 | 185.1 | 175.3 | 192.1 ± 55.7 | |
| In vivo Formed DPMA Metabolite | Fm(%)3-a | 0.72 | 0.64 | 0.84 | 1.10 | 5.30 | 1.72 ± 2.01 |
| Fm′ (%)b | 0.72 | 0.66 | 0.86 | 1.11 | 5.56 | 1.78 ± 2.12 | |
| MRT (min) | 220.3 | 243.3 | 368.3 | 281.0 | 378.3 | 298.2 ± 71.9 | |
| Fetal | |||||||
| DPHM (or [2H10]-DPHM) | CLtb(ml/min/kg) | 465.0 | 304.6 | 294.1 | 128.7 | 235.6 | 285.6 ± 122.2 |
| Vd ss(l/kg) | 18.1 | 10.5 | 13.4 | 10.6 | 13.0 | 13.1 ± 3.1 | |
| T 1/2β(min) | 14.4 | 19.1 | 21.5 | 65.4 | 44.9 | 33.1 ± 21.6 | |
| MRT (min) | 38.9 | 34.5 | 45.7 | 82.0 | 55.3 | 51.3 ± 18.9 | |
| Preformed DPMA Metabolite | CLtb(ml/min/kg) | 0.50 | 0.38 | 0.38 | 0.19 | 0.40 | 0.37 ± 0.11 |
| Vd ss(l/kg) | 0.43 | 0.40 | 0.48 | 0.32 | 0.37 | 0.40 ± 0.06 | |
| T 1/2β(min) | 630.4 | 762.3 | 895.3 | 1180.1 | 861.9 | 866.0 ± 203.6 | |
| MRT (min) | 868.4 | 1049.6 | 1237.3 | 1662.5 | 937.4 | 1151.1 ± 318.1 | |
| In vivo Formed DPMA Metabolite | Fm(%)3-a | 0.46 | 0.20 | 0.39 | 0.22 | 0.30 | 0.32 ± 0.11 |
| Fm′ (%)b | 1.80 | 0.33 | 0.83 | 0.58 | 0.81 | 0.87 ± 0.56 | |
| MRT (min) | 1008.3 | 1140.7 | 1407.1 | 2103.5 | 1349.3 | 1401.8 ± 423.7 |
↵3-a In vivo formation clearance of the metabolite as a fraction of total body clearance or fraction of parent drug dose converted to metabolite in vivo. b In vivo formation clearance of the metabolite as a fraction of non-placental clearance.