Table 2.
Plasma Pharmacokinetic Data by Volunteer and Metabolite*
| Volunteer | S. Front | M1 | Diol | M5 | M6 | M7 | M8 | DBC | Sum | |
|---|---|---|---|---|---|---|---|---|---|---|
| Tmax (h) | V5 | 3.0 | - | 3.0 | 3.0 | 3.0 | 1.0 | - | 3.0 | 3.0 |
| V8 | 2.5 | - | 1.0 | 1.0 | 1.0 | 1.0 | - | 1.0 | 1.0 | |
| V9 | 1.5 | 2.0 | 1.5 | 1.5 | 1.5 | 1.5 | 1.5 | 1.5 | 1.5 | |
| V13 | 3.0 | 1.0 | 1.5 | 1.5 | 1.5 | 1.5 | 3.0 | 3.0 | 3.0 | |
| Avg. | 2.5 | 1.5 | 1.7 | 1.7 | 1.7 | 1.2 | 2.2 | 2.1 | 2.1 | |
| S.D. | 0.7 | 0.7 | 0.9 | 0.9 | 0.9 | 0.3 | 1.1 | 1.0 | 1.0 | |
|
|
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| Cmax (fg/mL) | V5 | 3.8 | ND | 3.6 | 2.7 | 2.0 | 1.6 | ND | 3.0 | 73.0 |
| V8 | 6.9 | ND | 2.4 | 1.1 | 1.2 | 0.7 | ND | 27.9 | 36.8 | |
| V9 | 3.3 | 0.8 | 3.1 | 1.3 | 2.7 | 2.0 | 4.0 | 35.0 | 52.9 | |
| V13 | 2.7 | 0.5 | 0.6 | 0.3 | 1.2 | 0.7 | 1.9 | 7.3 | 13.1 | |
| Avg. | 4.2 | 0.7 | 2. 6 | 1.3 | 1.8 | 1.2 | 3.0 | 18.5 | 44.0 | |
| S.D. | 1.9 | 0.2 | 1.3 | 1.0 | 0.7 | 0.7 | 1.4 | 15.9 | 25.3 | |
|
|
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| α-AUC0–8 hr (fg/h/mL) | V5 | 17.9 | ND | 15.0 | 8.8 | 8.5 | 2.8 | ND | 220.7 | 277.0 |
| V8 | 22.3 | ND | 8.1 | 3.0 | 0.2 | 1.1 | ND | 57.0 | 99.6 | |
| V9 | 9.6 | 1.8 | 13.5 | 2.0 | 5.7 | 4.0 | 6.4 | 153.3 | 299.0 | |
| V13 | 38.0 | 1.2 | 11.0 | 1.3 | 8.6 | 2.0 | 14.0 | 83.9 | 169.3 | |
| Avg. | 22.0 | 1.5 | 11.9 | 4.0 | 5.8 | 2.5 | 10.2 | 128.7 | 211.3 | |
| S.D. | 11.0 | 0.4 | 3.0 | 3.3 | 3.9 | 1.2 | 5.4 | 73.5 | 93.5 | |
|
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| α-Kel (fg/h) | V5 | 1.0 | ND | 0.2 | 0.3 | 0.3 | 0.7 | ND | 0.3 | 0.3 |
| V8 | 0.2 | ND | 0.2 | 0.2 | 0.7 | 0.9 | ND | 0.8 | 0.6 | |
| V9 | 0.4 | 0.9 | 0.1 | 0.3 | 0.9 | 0.6 | 1.1 | 0.3 | 0.1 | |
| V13 | 0.2 | 1.0 | 0.5 | 1.0 | 0.2 | 0.2 | 0.3 | 0.4 | 0.3 | |
| Avg. | 0.5 | 1.0 | 0.3 | 0.5 | 0.5 | 0.6 | 0.7 | 0.4 | 0.3 | |
| S.D. | 0.4 | 0.1 | 0.2 | 0.3 | 0.3 | 0.3 | 0.5 | 0.2 | 0.2 | |
|
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| α-T½ (h) | V5 | 0.7 | ND | 3.4 | 2.0 | 2.2 | 0.9 | ND | 2.4 | 2.7 |
| V8 | 3.1 | ND | 3.3 | 3.7 | 1.0 | 0.7 | ND | 0.9 | 1.0 | |
| V9 | 1.7 | 0.7 | 5.0 | 2.0 | 0.7 | 1.2 | 0.6 | 2.0 | 8.6 | |
| V13 | 3.0 | 0.7 | 1.4 | 0.7 | 2.9 | 3.2 | 2.2 | 1.9 | 2.4 | |
| Avg. | 2.1 | 0.7 | 3.3 | 2.1 | 1.7 | 1.5 | 1.4 | 1.8 | 3.7 | |
| S.D. | 1.1 | 0.0 | 1.5 | 1.2 | 1.0 | 1.1 | 1.1 | 0.6 | 3.4 | |
*
The pharmacokinetic parameters of plasma [14C]-DBC UPLC-AMS data was determined using non-compartmental computational models. Where insufficient >LLOQ data was available, PK analysis was not determined (ND).