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. Author manuscript; available in PMC: 2013 Jan 31.
Published in final edited form as: Clin Pharmacol Ther. 2011 May 11;90(1):100–108. doi: 10.1038/clpt.2011.59

Table 2.

Oral midazolam and alfentanil pharmacokinetic and pupil effect parameters

Control rifampin
5 mg 10 mg 25 mg 75 mg
Oral midazolam
 Cmax (ng/ml) 15 ± 5 12 ± 4 14 ± 6 7.6 ± 3.0* 5.1 ± 1.9*
 Tmax (hr) 0.7 ± 0.4 0.6 ± 0.4 0.5 ± 0.2 0.5 ± 0.2 0.5 ± 0.3
 AUC0-∞ (ng•hr •ml−1) 35.0 ± 12.8 26.8 ± 8.4* 22.7 ± 6.9* 13.3 ± 3.3* 8.1 ± 1.9*
 AUC0-∞ ratio 0.80 ± 0.19* 0.68 ± 0.17* 0.40 ± 0.10* 0.25 ± 0.09*
 (geometric mean, 90% CI) 0.78 (0.70,0.87) 0.66 (0.59,0.74) 0.39 (0.35,0.44) 0.24 (0.20,0.28)
 CL/F (ml•kg−1•min−1) 23.0 ± 10.0 28.4 ± 10.0* 33.4 ± 12.8* 56.5 ± 19.4* 95.5 ± 35.8*
 Elimination t1/2 (hr) 3.0 ± 0.9 2.7 ± 0.8 2.4 ± 1.0* 2.3 ± 0.9* 1.7 ± 0.5*
 Vz/F (L/kg) 5.6 ± 2.0 6.4 ± 2.4 6.5 ± 2.4 11.1 ± 5.2* 14.5 ± 8.6*
 Foral 0.29 ± 0.10 0.26 ± 0.07 0.25 ± 0.12 0.18 ± 0.05* 0.11 ± 0.04*
 EG 0.53 ± 0.17 0.49 ± 0.19 0.51 ± 0.22 0.54 ± 0.15 0.68 ± 0.14*
 C4 hr (ng/ml) 2.6 ± 1.0 1.9 ± 0.8* 1.4 ± 0.5* 0.9 ± 0.3* 0.5 ± 0.3*
 C4 hr ratio 0.73 ± 0.21* 0.60 ± 0.19* 0.37 ± 0.13* 0.21 ± 0.10*
 (geometric mean, 90% CI) 0.74 (0.65,0.84) 0.57 (0.49,0.66) 0.35 (0.29,0.41) 0.19 (0.16,0.24)
 C5 hr (ng/ml) 1.9 ± 0.7 1.4 ± 0.6* 1.1 ± 0.4* 0.6 ± 0.2* 0.3 ± 0.1 *
 C5 h ratio 0.76 ±0.21* 0.58 ± 0.16* 0.32 ± 0.11* 0.19 ± 0.08*
 (geometric mean, 90% CI) 0.73 (0.65,0.84) 0.56 (0.48,0.64) 0.31 (0.27,0.36) 0.17 (0.14,0.21)
Oral alfentanil
 Cmax (ng/ml) 51 ± 21 44 ± 15 44 ± 17 25 ± 12* 13 ± 10*
 Tmax (hr) 1.0 ± 0.6 1.0 ± 0.6 0.6 ± 0.2 0.6 ± 0.5 0.6 ± 0.5
 AUC0-∞ (ng•hr •ml−1) 146 ± 84 101 ± 42* 81 ± 41* 43 ± 27* 18 ± 13*
 AUC0-∞ ratio 0.74 ± 0.16* 0.61 ± 0.23* 0.30 ± 0.10* 0.13 ± 0.06*
 (geometric mean, 90% CI) 0.73 (0.66, 0.80) 0.57 (0.47,0.69) 0.28 (0.24, 0.34) 0.12 (0.10,0.15)
 CL/F (ml•kg−1•min−1) 11.1 ± 5.7 14.8 ± 7.2* 19.7 ± 11.6* 41.9 ± 28.7* 91.7 ± 44.6*
 Elimination t1/2 (hr) 1.4 ± 0.5 1.2 ± 0.3* 1.1 ± 0.3* 1.0 ± 0.2* 0.8 ± 0.2*
 Vz/F (L/kg) 1.2 ± 0.4 1.4 ± 0.3 1.7 ± 0.8* 3.2 ± 1.9* 6.1 ± 2.6*
 Foral 0.37 ± 0.12 0.33 ± 0.09 0.29 ± 0.12* 0.19 ± 0.08* 0.09 ± 0.04*
 EG 0.51 ± 0.15 0.54 ± 0.13 0.56 ± 0.18 0.68 ± 0.14* 0.83 ± 0.06*
 C2 hr (ng/ml) 35 ± 23 25 ± 11* 18 ± 11* 10 ± 10* 4 ± 3*
 C2 hr ratio 0.78 ± 0.17* 0.50 ± 0.16* 0.26 ± 0.11* 0.10 ± 0.04*
 (geometric mean, 90% CI) 0.76 (0.69,0.85) 0.47 (0.39,0.58) 0.24 (0.19,0.30) 0.09 (0.08,0.11)
 C4 hr (ng/ml) 15 ± 12 7 ± 5* 6 ± 7* 2 ± 2* 0.7 ± 0.6*
 C4 hr ratio 0.58 ± 0.16* 0.42 ± 0.25* 0.16 ± 0.07* 0.05 ± 0.03*
 (geometric mean, 90% CI) 0.56 (0.49,0.64) 0.37 (0.29,0.47) 0.14 (0.12,0.17) 0.05 (0.03,0.06)
Oral alfentanil pupil miosis
 maximum (mm) 3.1 ± 1.3 2.5 ± 1.0* 2.1 ± 1.2* 1.5 ± 1.3* 0.9 ± 0.7*
 AUEC0-last (mm•hr) 5.0 ± 4.8 3.1 ± 1.8* 2.0 ± 3.0* 1.8 ± 3.0* 0.9 ± 1.3*
 AUEC0-∞ (mm•hr) 5.4 ± 5.1 3.5 ± 2.0* 2.4 ± 3.5* 2.6 ± 3.5* 1.2 ± 1.5*
 AUEC0-∞ ratio 0.9 ± 0.5 0.4 ± 0.2* 0.4 ± 0.2* 0.3 ± 0.4*
 (geometric mean, 90% CI) 0.78 (0.60, 1.00) 0.32 (0.22,0.46) 0.30 (0.18,0.50) 0.10 (0.05,0.22)

All subjects received 3 mg oral MDZ, followed by 75 μg/kg oral ALF. Results 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, maximum concentration; Tmax, Time of maximum concentration; AUC0-∞, area under plasma concentration–time curve extrapolated to infinity; C2 hr, C4 hr and C5 hr, plasma concentration 2, 4 or 5 hr after dosing; CL/F, apparent oral clearance; t1/2, half-life; Vz/F, apparent volume of distribution based on the terminal phase; Foral, oral bioavailability; EG, intestinal extraction; AUEC0-last, area under effect (miosis) curve to last time point measured; AUEC0-∞, area under effect (miosis) curve extrapolated to infinity.

*

Significantly different from control (p<0.05)