. Author manuscript; available in PMC: 2013 Feb 28.

Published in final edited form as: Clin Pharmacol Ther. 2011 Feb 23;89(4):562–570. doi: 10.1038/clpt.2010.313

Table 2.

Oral alfentanil pharmacokinetic parameters

	Control	Rifampin	Grapefruit	Ketoconazole
Sequential dosing
C_max/D (ng •ml⁻¹ •mg⁻¹)	12±6	1.5±0.9^a	13±7	33±10^a
T_max (hr)	1.0±0.8	0.4±0.2	1.4±1.0	1.3±1.0
AUC_0-∞/D (ng •hr •ml⁻¹ •mg⁻¹)	27±17	1.6±0.8	45±27	253±178^a
AUC_0-∞/D ratio (geometric mean, 90% CI)		0.06 (0.05,0.07)	1.7 (1.5,1.9)	9.2 (8.0,10.7)
CL/F (ml•kg⁻¹•min⁻¹)	11.1±6.8	168±74^a	6.4±3.8^a	1.2±0.6^a
Elimination t_1/2 (hr)	1.2±0.3	0.6±0.1^a	1.4±0.5	4.7±2.1^a
F_oral	0.43±0.09	0.08±0.03^a	0.76±0.13^a	0.83±0.11^a
E_G	0.42±0.07	0.81±0.06^a	0.02±0.04^a	0.14±0.08^a
C_{4 hr}/D (ng • ml⁻¹ •mg⁻¹)	2.2±2.0	0.02±0.03^a	4.7±2.9^a	20.7±8.7^a
C_{4 hr}/D ratio (geometric mean, 90% CI)		0.01 (0.00,0.02)	2.3 (1.9,2.8)	11.6 (7.5, 17.9)
Simultaneous dosing
C_max/D (ng •ml⁻¹ •mg⁻¹)	7.1±3.0^b	0.9±0.5^a,^b	13±9^a	36±20^a
T_max (hr)	1.4±0.4	0.6±0.2	1.6±1.3	1.7±0.9
AUC_0-∞/D (ng •hr •ml⁻¹ •mg⁻¹)	22±14	1.1±0.5	46±21	298±255^a,^b
AUC_0-∞/D ratio (geometric mean, 90% CI)		0.06 (0.01,0.22)	2.2 (1.9,2.5)	12.0 (6.2,23.3)
CL/F (ml•kg⁻¹•min⁻¹)	13.6±8.2	224±101^a,^b	6.0±3.7^a	1.2±0.8^a
Elimination t_1/2 (hr)	1.4±0.5	0.6±0.1^a	1.8±0.8	5.2±1.9^a
F_oral	0.41±0.11	0.06±0.03^a	0.76±0.14^a	0.95±0.08^a,^b
E_G	0.42±0.11	0.74±0.12^a	0.06±0.10^a	0.02±0.04^a
C_{4 hr}/D (ng • ml⁻¹ •mg⁻¹)	2.2±1.1	0.03±0.02^a	5.6±2.4^a	23.6±16.7^a
C_{4 hr}/D ratio (geometric mean, 90% CI)		0.01 (0.01,0.02)	2.8 (2.2, 3.7)	11.3 (8.4,15.1)

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. C_max/D, dose-normalized maximum concentration; T_max, time of maximum concentration; AUC_0-∞/D, dose-normalized area under plasma concentration–time curve extrapolated to infinity; CL/F, apparent oral clearance; t_1/2, half-life; F_oral, oral bioavailability; E_G, intestinal extraction; C_{4 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)