TABLE 1

Pharmacokinetic variables for ATV and its metabolites in rats (n = 5) after a single oral dose (10 mg/kg) or intravenous dose (2 mg/kg) of ATV with and without RIF given as a bolus intravenous dose (20 mg/kg)

Data are mean values ± S.D. (n = 5); tmax data are given as median and range.

Variable
Intravenous
Oral
ATV Alone
With RIF
ATV Alone
With RIF
ATV
    Cmax (μM) 1.69 ± 0.63a 2.48 ± 1.10a 0.21 ± 0.36 0.65 ± 0.46*
    tmax (min) a a 20 (10-60) 30 (30-120)
    t1/2 (min) 288 ± 83 292 ± 128 N.D. 245 ± 122
    AUC0-12 h (μM min) 68.1 ± 16.2 89.7 ± 23.5 19.6 ± 8.8 68.2 ± 26.3**
    AUC0-∞ (μM min) 78.7 ± 18.9 107 ± 19* 20.6 ± 8.8 71.8 ± 26.5**
2-OH ATV
    Cmax (μM) 0.013 ± 0.008 0.040 ± 0.015** 0.021 ± 0.011 0.055 ± 0.048*
    tmax (min) 10 (10-30) 20 (10-30) 60 (20-60) 30 (30-120)
    AUC0-2 h (μM min) 0.71 ± 0.27 2.84 ± 0.91** 1.72 ± 1.21 5.19 ± 2.91*
4-OH ATV
    Cmax (μM) 0.004 ± 0.001 0.027 ± 0.021** 0.012 ± 0.020 0.030 ± 0.031*
    tmax (min) 10 (10-30) 10 (10-30) 30 (10-60) 60 (30-120)
    AUC0-4 h (μM min)
0.64 ± 0.31
2.22 ± 0.52***
0.81 ± 0.61
5.52 ± 3.59*

  • N.D., not determinable due to assay limits of quantitation.

  • ↵* p < 0.05; ** p < 0.01; *** p < 0.001 compared with values for the same dosing route in the absence of RIF.

  • ↵ a For intravenous parent ATV dosing, the first measured time point was at 5 min.