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).
| Control | Nelfinavir | Ritonavir | Rifampin | |||||
|---|---|---|---|---|---|---|---|---|
| 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 14 | AUC0-∞ (h · μg/ml) | 56.7 ± 46.6 | 30.8 ± 12.9 | 0.49 (0.29–0.84) | 13.90 ± 6.8 | 0.35 (0.26–0.45) | 22.6 ± 7.3 | 0.47 (0.38–0.58) |
| Clearance (ml/min) | 85.4 ± 45.0 | 131 ± 69.0 | 2.03 (1.20–3.45) | 285 ± 128 | 2.90 (2.22–3.80) | 168 ± 73.0 | 2.14 (1.73–2.66) | |
| Clform (ml/min) | 64.3 ± 44.5 | 108 ± 71.2 | 2.13 (1.20–3.81) | 211 ± 88.8 | 2.89 (2.02–4.12) | 132 ± 76.4 | 2.23 (1.79–2.78) | |
| CYP2B6 (Bupropion) n = 9 | AUC0-∞ (h · ng/ml) | 1786 ± 1543 | 1648 ± 1117 | 1.10 (0.75–1.61) | 1201 ± 775 | 0.98 (0.57–1.71) | 962 ± 761 | 0.60 (0.50–0.73) |
| Clearance (l/min) | 5.66 ± 8.80 | 5.49 ± 11.2 | 0.91 (0.62–1.34) | 2.82 ± 1.39 | 1.01 (0.58–1.77) | 8.97 ± 15.7 | 1.66 (1.36–2.02) | |
| Clform (ml/min) | 192 ± 347 | 279 ± 590 | 1.80 (1.08–3.00) | 174 ± 149 | 2.40 (1.13–5.09) | 619 ± 1310 | 3.98 (2.33–6.80) | |
| (S,S)-OH-BUP/(S)-BUP UR | 5.7 ± 5.3 | 9.0 ± 7.5 | 1.77 (1.18–1.84) | 17.7 ± 16.1 | 3.30 (1.97–5.53) | 34.4 ± 34.3 | 4.84 (2.88–8.12) | |
| CYP2C9 (Tolbutamide) n = CON 16, NFV 7, RTV 8, RIF 15 | AUC0-∞ (h · μg/ml) | 596 ± 203 | 455 ± 229 | 0.68 (0.54–0.85) | 295 ± 106 | 0.50 (0.43–0.58) | 216 ± 101 | 0.34 (0.28–0.42) |
| Clearance (ml/min) | 15.7 ± 6.0 | 21.6 ± 8.3 | 1.47 (1.18–1.84) | 33.2 ± 16.7 | 2.00 (1.73–2.31) | 48.3 ± 25.4 | 2.94 (2.39–3.62) | |
| Clform (ml/min) | 6.92 ± 3.59 | 9.80 ± 3.86 | 1.34 (1.13–1.58) | 13.4 ± 9.61 | 1.80 (1.56–2.08) | 19.5 ± 11.1 | 2.55 (2.02–3.22) | |
| CYP2D6 (Dextromethorphan) n = CON 15, NFV 7, RTV 7, RIF 14 | AUC0-∞ (h · ng/ml) | 39.4 ± 56.0 | 46.3 ± 58.4 | 0.87 (0.41–1.82) | 65.1 ± 67.0 | 4.54 (2.35–8.77) | 10.3 ± 19.0 | 0.27 (0.17–0.42) |
| Clearance (ml/min) | 97.1 ± 124 | 102 ± 157 | 1.16 (0.55–2.42) | 19.8 ± 26.3 | 0.22 (0.11–0.43) | 285 ± 292 | 3.73 (2.38–5.86) | |
| DOR/DEX | 3.78 ± 3.99 | 1.17 ± 1.30 | 0.64 (0.35–1.20) | 0.94 ± 1.44 | 0.11 (0.04–0.31) | 1.97 ± 2.36 | 0.50 (0.28–0.88) | |
| DOR/DEX UR Ratio | 306 ± 313 | 375 ± 650 | 0.85 (0.30–2.41) | 37.1 ± 34.1 | 0.13 (0.05–0.32) | 493 ± 407 | 1.77 (1.07–2.94) | |
| CYP3A? (Dextromethorphan) n = CON 15, NFV 7, RTV 8, RIF 15 | 3MM/DEX UR Ratio | 0.72 ± 0.75 | 0.76 ± 1.00 | 1.00 (0.44–2.26) | 0.25 ± 0.19 | 0.46 (0.20–1.09) | 1.49 ± 1.35 | 2.48 (1.28–4.80) |
GMR (treatment/control); CON, control.