TABLE 2

In vivo CYP1A2, CYP2B6, CYP2C9, or CYP2D6 activity measured by disposition of caffeine, bupropion, tolbutamide, or dextromethorphan, respectively, before and after multiple dose administration of nelfinavir, ritonavir, or rifampin

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

ControlNelfinavirRitonavirRifampin
Average ± S.D.Average ± S.D.GMR (90% CI)Average ± S.D.GMR (90% CI)Average ± S.D.GMR (90% CI)
CYP1A2 (Caffeine) n = CON 14, NFV 7, RTV 6, RIF 14AUC0-∞ (h · μg/ml)56.7 ± 46.630.8 ± 12.90.49 (0.29–0.84)13.90 ± 6.80.35 (0.26–0.45)22.6 ± 7.30.47 (0.38–0.58)
Clearance (ml/min)85.4 ± 45.0131 ± 69.02.03 (1.20–3.45)285 ± 1282.90 (2.22–3.80)168 ± 73.02.14 (1.73–2.66)
Clform (ml/min)64.3 ± 44.5108 ± 71.22.13 (1.20–3.81)211 ± 88.82.89 (2.02–4.12)132 ± 76.42.23 (1.79–2.78)
CYP2B6 (Bupropion) n = 9AUC0-∞ (h · ng/ml)1786 ± 15431648 ± 11171.10 (0.75–1.61)1201 ± 7750.98 (0.57–1.71)962 ± 7610.60 (0.50–0.73)
Clearance (l/min)5.66 ± 8.805.49 ± 11.20.91 (0.62–1.34)2.82 ± 1.391.01 (0.58–1.77)8.97 ± 15.71.66 (1.36–2.02)
Clform (ml/min)192 ± 347279 ± 5901.80 (1.08–3.00)174 ± 1492.40 (1.13–5.09)619 ± 13103.98 (2.33–6.80)
(S,S)-OH-BUP/(S)-BUP UR5.7 ± 5.39.0 ± 7.51.77 (1.18–1.84)17.7 ± 16.13.30 (1.97–5.53)34.4 ± 34.34.84 (2.88–8.12)
CYP2C9 (Tolbutamide) n = CON 16, NFV 7, RTV 8, RIF 15AUC0-∞ (h · μg/ml)596 ± 203455 ± 2290.68 (0.54–0.85)295 ± 1060.50 (0.43–0.58)216 ± 1010.34 (0.28–0.42)
Clearance (ml/min)15.7 ± 6.021.6 ± 8.31.47 (1.18–1.84)33.2 ± 16.72.00 (1.73–2.31)48.3 ± 25.42.94 (2.39–3.62)
Clform (ml/min)6.92 ± 3.599.80 ± 3.861.34 (1.13–1.58)13.4 ± 9.611.80 (1.56–2.08)19.5 ± 11.12.55 (2.02–3.22)
CYP2D6 (Dextromethorphan) n = CON 15, NFV 7, RTV 7, RIF 14AUC0-∞ (h · ng/ml)39.4 ± 56.046.3 ± 58.40.87 (0.41–1.82)65.1 ± 67.04.54 (2.35–8.77)10.3 ± 19.00.27 (0.17–0.42)
Clearance (ml/min)97.1 ± 124102 ± 1571.16 (0.55–2.42)19.8 ± 26.30.22 (0.11–0.43)285 ± 2923.73 (2.38–5.86)
DOR/DEX3.78 ± 3.991.17 ± 1.300.64 (0.35–1.20)0.94 ± 1.440.11 (0.04–0.31)1.97 ± 2.360.50 (0.28–0.88)
DOR/DEX UR Ratio306 ± 313375 ± 6500.85 (0.30–2.41)37.1 ± 34.10.13 (0.05–0.32)493 ± 4071.77 (1.07–2.94)
CYP3A? (Dextromethorphan) n = CON 15, NFV 7, RTV 8, RIF 153MM/DEX UR Ratio0.72 ± 0.750.76 ± 1.001.00 (0.44–2.26)0.25 ± 0.190.46 (0.20–1.09)1.49 ± 1.352.48 (1.28–4.80)
  • GMR (treatment/control); CON, control.