TABLE 1

Pharmacokinetic parameters of digoxin before (control) and after nelfinavir, ritonavir, or rifampin treatment

Bold values are statistically significant (90% CI does not include 1.00).

ParameterControlaNelfinavirbRitonavircRifampind
Average ± S.D.Average ± S.D.GMR (90% CI)Average ± S.D.GMR (90% CI)Average ± S.D.GMR (90% CI)
Study 1: staggered administration
    Cmax, ng/ml1.34 ± 0.531.44 ± 0.961.05 (0.63–1.74)1.59 ± 0.800.98 (0.61–1.57)1.02 ± 0.380.78 (0.57–1.06)
    Tmax, h1.66 ± 0.772.56 ± 2.471.32 (0.66–2.64)2.13 ± 1.031.10 (0.75–1.62)1.82 ± 0.851.04 (0.78–1.38)
    AUC0–4 h, h · ng/ml2.96 ± 0.973.08 ± 1.641.05 (0.63–1.74)4.13 ± 2.151.10 (0.71–1.73)2.26 ± 0.670.79 (0.62–1.02)
    AUC0–24 h, h · ng/ml8.66 ± 2.579.46 ± 2.931.23 (1.00–1.48)12.7 ± 6.221.16 (0.81–1.66)6.83 ± 1.680.81 (0.69–0.96)
    Clrenal, ml/min146 ± 43.3141 ± 65.40.87 (0.65–1.16)115 ± 39.10.79 (0.67–0.93)162 ± 51.41.06 (0.95–1.19)
Study 2: simultaneous administration (24 h after BUP)
    Cmax, ng/ml1.24 ± 0.351.66 ± 0.811.23 (0.91–1.68)1.55 ± 0.711.16 (0.86–1.57)2.12 ± 1.041.55* (1.20–1.99)
    Tmax, h1.56 ± 0.642.21 ± 1.041.38 (0.93–2.05)2.30 ± 0.891.54 (1.22–1.94)1.56 ± 0.890.93 (0.68–1.26)
    AUC0–4 h, h · ng/ml2.47 ± 0.493.14 ± 1.681.02 (0.59–1.74)3.06 ± 1.411.13 (0.85–1.49)3.71 ± 1.721.37* (1.05–1.80)
    AUC0–24 h, h · ng/ml5.45 ± 1.99*7.35 ± 3.501.20 (0.90–1.60)7.59 ± 3.141.37 (1.11–1.70)7.08 ± 3.251.25* (0.93–1.70)
    Clrenal, ml/min258 ± 64.9*236 ± 83.00.92 (0.75–1.13)168 ± 46.30.64 (0.55–0.75)225 ± 59.80.87 (0.78–0.97)
  • GMR, geometric mean ratio.

  • * Values are significantly different between Studies 1 and 2 (unpaired t test, p < 0.05).

  • a Study 1 n = 16, Study 2 n = 9;

  • b Study 1 n = 7, Study 2 n = 9;

  • c Study 1 n = 8, Study 2 n = 9;

  • d Study 1 n = 16, Study 2 n = 9.