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.