Table 1.
Intravenous alfentanil pharmacokinetic parameters
| Control | Rifampin | Grapefruit | Ketoconazole | |
|---|---|---|---|---|
| Sequential dosing | ||||
| Cmax/D (ng •ml−1 •mg−1) | 80±40 | 54±10 | 59±31 | 73±19 |
| AUC0-∞/D (ng •hr •ml−1 •mg−1) | 59±27 | 21±8a | 57±30 | 291±159a |
| AUC0-∞/D ratio (geometric mean, 90% CI) | 0.4 (0.3,0.4) | 1.0 (0.9,1.0) | 4.8 (4.3,5.3) | |
| CLIV (ml•kg−1•min−1) | 4.3±1.8 | 11.3±3.4a | 4.5±2.0 | 0.9±0.4a |
| Elimination t1/2 (hr) | 1.4±0.4 | 0.9±0.1a | 1.5±0.4 | 5.0±1.6a |
| Vss (L/kg) | 0.39±0.13 | 0.48±0.16a | 0.46±0.14a | 0.34±0.10 |
| EH | 0.26±0.09 | 0.71±0.22a | 0.28±0.11 | 0.05±0.02a |
| C4 hr/D (ng • ml−1 •mg−1) | 3.1±2.3 | 0.3±0.1a | 2.9±1.8 | 21.6±9.6a |
| C4 hr/D ratio (geometric mean, 90% CI) | 0.1 (0.1,0.2) | 1.0 (0.8,1.1) | 7.8 (5.6,11.0) | |
| Simultaneous dosing | ||||
| Cmax/D (ng •ml−1 •mg−1) | 58±15b | 57±8 | 55±12 | 73±26 |
| AUC0-∞/D (ng •hr •ml−1 •mg−1) | 51±19 | 18±3a | 58±22 | 302±244a |
| AUC0-∞/D ratio (geometric mean, 90% CI) | 0.4 (0.2,0.7) | 1.2 (1.1,1.2) | 5.0 (2.9,8.6) | |
| CLIV (ml•kg−1•min−1) | 4.8±1.8 | 12.1±2.4a | 4.2±1.6 | 1.1±0.7a |
| Elimination t1/2 (hr) | 1.4±0.4 | 0.7±0.1a | 1.6±0.5 | 5.4±2.1a |
| Vss (L/kg) | 0.45±0.11 | 0.56±0.09a | 0.48±0.13 | 0.38±0.11a |
| EH | 0.30±0.10 | 0.76±0.16a | 0.25±0.08 | 0.06±0.03a |
| C4 hr/D (ng • ml−1 •mg−1) | 2.8±1.6 | 0.3±0.0a | 3.8±1.7b | 21.6±14.6a |
| C4 hr/D ratio (geometric mean, 90% CI) | 0.1 (0.1,0.2) | 1.4 (1.1,1.7) | 7.6 (5.2,11.0) | |
For sequential dosing subjects received 1 mg IV d0-ALF followed 3 hr later by 4 mg oral d3-ALF, except after ketoconazole pretreatment, where they received 0.5 mg IV d0-ALF and 1 mg oral d3-ALF. For simultaneous dosing subjects received IV d0-ALF and oral d3-ALF at the same time, in the same doses as for sequential administration. Results (n=6) are the arithmetic mean ± SD, except AUC ratios and single-point concentration ratios, which are also shown as the geometric mean and 90% confidence interval. Cmax/D, dose-normalized maximum concentration; AUC0-∞/D, dose-normalized area under plasma concentration–time curve extrapolated to infinity; CLIV, systemic clearance; t1/2, half-life; Vss, steady state volume of distribution; EH, hepatic extraction; C4 hr/D, dose-normalized plasma concentration 4 hr after dosing;
Significantly different from control (p<0.05)
Significantly different vs sequential dosing (p<0.05)