Pharmacokinetic parameters of drug-related radioactivity, atevirdine,N-desethyl atevirdine, and O-desmethyl atevirdine in male and female Sprague-Dawley rats after oral administration of [14C]atevirdine mesylate
| Time (hr) | Single-Dose | Multiple-Dose | ||||||
|---|---|---|---|---|---|---|---|---|
| 10 mg/kg | 100 mg/kg | 20 mg/kg/day | 200 mg/kg/day | |||||
| Male | Female | Male | Female | Male | Female | Male | Female | |
| Drug-related radioactivity | ||||||||
| AUC (μM · hr) | 44.1 ± 14.6 | 71.0 ± 18.3 | 403 ± 87 | 692 ± 160 | 40.9 ± 9.4 | 88.3 ± 11.1 | 483 ± 106 | 808 ± 86 |
| t max(hr) | 1.0 ± 0.0 | 1.0 ± 0.0 | 2.5 ± 1.7 | 4.0 ± 0.0 | 1.0 ± 0.0 | 1.0 ± 0.0 | 1.8 ± 1.5 | 3.3 ± 1.5 |
| C max (μM) | 10.9 ± 4.3 | 10.6 ± 1.7 | 48.8 ± 11.6 | 57.6 ± 10.9 | 10.7 ± 2.3 | 15.3 ± 2.6 | 65.8 ± 22.8 | 78.4 ± 13.5 |
| Atevirdine | ||||||||
| AUC (μM · hr) | 8.9 ± 4.8 | 33 ± 15 | 196 ± 43 | 507 ± 110 | 10.2 ± 3.4 | 48 ± 12 | 367 ± 44 | 1180 ± 390 |
| t max (hr) | 1.0 ± 0.0 | 1.0 ± 0.0 | 1.8 ± 1.5 | 4.0 ± 0.0 | 1.0 ± 0.0 | 1.0 ± 0.0 | 1.8 ± 1.5 | 1.8 ± 1.5 |
| C max(μM) | 4.3 ± 2.3 | 7.6 ± 1.6 | 28.8 ± 5.9 | 49.7 ± 9.7 | 4.8 ± 1.4 | 13.3 ± 2.9 | 67 ± 19 | 133 ± 34 |
| %2-a | 20 ± 10 | 44.9 ± 9.2 | 48.7 ± 1.7 | 73.6 ± 5.4 | ||||
| N-Desethyl atevirdine | ||||||||
| AUC (μM · hr) | 4.2 ± 2.0 | 3.76 ± 0.98 | 56 ± 18 | 56.9 ± 4.8 | 2.44 ± 0.56 | 4.34 ± 0.99 | 32 ± 16 | 81 ± 37 |
| t max(hr) | 1.0 ± 0.0 | 1.0 ± 0.0 | 1.8 ± 1.5 | 4.0 ± 0.0 | 1.0 ± 0.0 | 1.0 ± 0.0 | 3.3 ± 1.5 | 4.0 ± 0.0 |
| C max (μM) | 1.85 ± 0.90 | 0.75 ± 0.18 | 7.8 ± 2.3 | 6.7 ± 1.0 | 1.05 ± 0.18 | 1.04 ± 0.29 | 4.4 ± 2.1 | 9.8 ± 4.2 |
| %2-a | 9.4 ± 3.6 | 5.32 ± 0.43 | 13.6 ± 2.5 | 8.6 ± 2.2 | ||||
| O-Desmethyl atevirdine | ||||||||
| AUC (μM · hr) | 2.2 ± 1.3 | 11.9 ± 2.1 | 13.7 ± 2.1 | 46 ± 22 | 1.78 ± 0.68 | 17.2 ± 3.5 | 18.2 ± 2.3 | 52 ± 18 |
| t max(hr) | 1.0 ± 0.0 | 2.5 ± 1.7 | 4.0 ± 0.0 | 12.0 ± 0.0 | 1.0 ± 0.0 | 3.0 ± 1.7 | 0.75 ± 0.50 | 0.25 ± 0.50 |
| C max (μM) | 0.70 ± 0.30 | 1.18 ± 0.16 | 1.44 ± 0.42 | 2.51 ± 0.99 | 0.57 ± 0.13 | 1.57 ± 0.41 | 2.14 ± 0.51 | 3.99 ± 0.85 |
| %2-a | 4.6 ± 2.2 | 17.2 ± 2.2 | 3.50 ± 0.91 | 6.6 ± 2.2 | ||||
↵2-a Percentage of atevirdine, N-desethyl atevirdine, and O-desmethyl atevirdine in circulation. Values were calculated from the respective AUCs relative to radiochemical AUC of plasma.