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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 1.

Intravenous midazolam and alfentanil pharmacokinetic and pupil effect parameters

Control Rifampin
5 mg 10 mg 25 mg 75 mg
IV midazolam
 Cmax (ng/ml) 62 ± 29 64 ± 26 66 ± 19 52 ± 23 82 ± 34
 AUC0-∞ (ng •hr •ml−1) 40.9 ± 7.6 34.0 ± 6.5* 30.7 ± 4.5* 25.2 ± 3.6* 24.1 ± 4.5*
 AUC0-∞ ratio 0.84± 0.13* 0.77 ± 0.12* 0.63 ± 0.11* 0.60 ± 0.12*
 (geometric mean, 90% CI) 0.83 (0.77, 0.89) 0.76 (0.71, 0.83) 0.62 (0.57, 0.68) 0.59 (0.53,0.65)
 CLIV (ml•kg−1•min−1) 5.9 ± 1.6 7.1 ± 2.1* 7.6 ± 2.0* 9.3 ± 1.8* 9.8 ± 1.6*
 Elimination t1/2 (hr) 4.0 ± 2.0 3.0 ± 0.8* 2.8 ± 1.0* 2.6 ± 1.1* 1.9 ± 0.5*
 Vss (L/kg) 1.4 ± 0.5 1.3 ± 0.4 1.3 ± 0.4 1.5 ± 0.6 1.1 ± 0.3
 EH 0.38 ± 0.09 0.46 ± 0.11* 0.49 ± 0.10* 0.60 ± 0.09* 0.63 ± 0.09*
 C4 hr (ng/ml) 2.4 ± 0.5 2.2 ± 0.5 2.0 ± 1.3 1.3 ± 0.4* 0.2 ± 0.4*
 C4 hr ratio 0.88 ± 0.22 0.80 ± 0.36 0.56 ± 0.13* 0.48 ± 0.10*
 (geometric mean, 90% CI) 0.86 (0.76,0.96) 0.75 (0.63,0.89) 0.55 (0.49,0.61) 0.47 (0.43,0.52)
 C5 hr (ng/ml) 1.9 ± 0.6 1.6 ± 0.4 1.7 ±1.1 1.0 ± 0.2* 0.9 ± 0.4*
 C5 hr ratio 0.87 ± 0.23 0.90 ± 0.48 0.55 ± 0.13* 0.50 ± 0.17*
 (geometric mean, 90% CI) 0.84 (0.74,0.96) 0.82 (0.68,1.0) 0.54 (0.48,0.61) 0.47 (0.41,0.55)
IV alfentanil
 Cmax (ng/ml) 102 ± 37 106 ± 35 107 ± 23 102 ± 27 105 ± 26
 AUC0-∞ (ng •hr •ml−1) 78.0 ± 30.7 61.7 ± 19.4* 55.5 ± 16.7* 44.0 ± 15.9* 37.0 ± 8.5*
 AUC0-∞ ratio 0.83 ± 0.16* 0.75 ± 0.15* 0.59 ± 0.12* 0.51 ± 0.12*
 (geometric mean, 90% CI) 0.81 (0.74,0.90) 0.73 (0.66,0.82) 0.57 (0.52, 0.63) 0.50 (0.44,0.56)
 CLIV (ml•kg−1•min−1) 3.7 ± 1.4* 4.4 ± 1.2* 4.9 ± 1.4* 6.3 ± 1.8* 7.1 ± 1.4*
 Elimination t1/2 (hr) 1.4 ± 0.5 1.2 ± 0.3* 1.1 ± 0.2* 1.0 ± 0.2* 0.8 ± 0.2*
 Vss (L/kg) 0.35 ± 0.06 0.35 ± 0.03 0.36 ± 0.03 0.39 ± 0.09 0.38 ± 0.05
 EH 0.24 ± 0.09* 0.28 ± 0.08* 0.32 ± 0.09* 0.40 ± 0.11* 0.46 ± 0.09*
 C2 hr (ng/ml) 11.8 ± 5.1 8.9 ± 3.5* 8.2 ± 3.4* 5.8 ± 3.4* 4.5 ± 1.8*
 C2 hr ratio 0.82 ± 0.27* 0.74 ± 0.23* 0.51 ± 0.17* 0.42 ± 0.13*
 (geometric mean, 90% CI) 0.78 (0.68,0.91) 0.71 (0.62,0.82) 0.48 (0.41,0.57) 0.40 (0.34,0.46)
 C4 hr (ng/ml) 4.4 ± 3.2 3.1 ± 2.2* 2.7 ± 1.9* 1.4 ± 1.1* 0.8 ± 0.4*
 C4 hr ratio 0.77 ± 0.28* 0.72 ± 0.51* 0.36 ± 0.15* 0.24 ± 0.15*
 (geometric mean, 90% CI) 0.73 (0.62,0.86) 0.62 (0.49,0.80) 0.34 (0.29,0.40) 0.21 (0.17,0.27)
IV alfentanil pupil miosis
 Maximum (mm) 4.3 ± 0.8 4.5 ± 0.8 4.4 ± 0.8 4.4 ± 0.8 4.5 ± 0.9
 AUEC0-last (mm•hr) 2.8 ± 2.7 2.8 ± 2.3 1.7 ± 0.9 1.3 ± 1.0 2.1 ± 1.4
 AUEC0-∞ (mm•hr) 3.7 ± 5.0 3.9 ± 4.0 2.0 ± 1.2 1.5 ± 1.2 2.5 ± 1.8
 AUEC0-∞ ratio 1.6 ± 1.9 1.0 ± 0.8 1.0 ± 1.0 1.2 ± 1.0
 (geometric mean, 90% CI) 1.1 (0.8, 1.6) 0.74 (0.51, 1.08) 0.53 (0.30,0.94) 0.83 (0.49,1.40)

All subjects received 1 mg IV MDZ, followed by 15 μg/kg IV 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; AUC0-∞, 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 and C5 hr, plasma concentration 4 or 5 hr after dosing; 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)