MDZ pharmacokinetic parameters before and after treatment with NFV, RTV, or RIF
Bold values are significantly different from control (P < 0.05, paired t test) or the 90% CI does not include unity.
| Control | Nelfinavir | Ritonavir | Rifampin | ||||
|---|---|---|---|---|---|---|---|
| Avg. ± S.D. | GMR (90% CI) | Avg. ± S.D. | GMR (90% CI) | Avg. ± S.D. | GMR (90% CI) | ||
| Study 2: midazolam simultaneously administered with NFV, RTV, or RIF | |||||||
| Oral | |||||||
| AUC0–∞ (h · ng/ml) | 25.7 ± 10.4 | 136 ± 33 | 5.8 (4.5–7.5) | 266 ± 99 | 10.5 (8.7–12.7) | 2.49 ± 0.74 | 0.10 (0.08–0.13) |
| Cloral (l/min) | 1.51 ± 0.6 | 0.26 ± 0.05 | 0.17 (0.13–0.22) | 0.14 ± 0.05 | 0.10 (0.08–0.12) | 14.5 ± 4.1 | 10.0 (7.7–12.9) |
| Cloral (ml · min−1 · kg−1) | 19.5 ± 8.3 | 3.36 ± 0.86 | 0.17 (0.13–0.22) | 1.85 ± 0.70 | 0.10 (0.08–0.12) | 185 ± 51.3 | 10.0 (7.7–12.9) |
| Clformation (l/min) | 1.10 ± 0.5 | 0.12 ± 0.04 | 0.11 (0.08–0.15) | 0.05 ± 0.02 | 0.05 (0.04–0.06) | 9.2 ± 2.9 | 8.8 (6.7–11.4) |
| t1/2 (h) | 4.7 ± 1.8 | 5.5 ± 2.5 | 1.2 (1.03–1.5) | 14 ± 7.7 | 2.9 (2.5–3.4) | 1.5 ± 0.6 | 0.33 (0.27–0.41) |
| Study 1: midazolam staggered administered with NFV, RTV, or RIF | |||||||
| Oral | |||||||
| AUC0–∞ (h · ng/ml) | 22.7 ± 9.4 | 77.4 ± 51.5 | 3.3 (1.9–5.5) | 188 ± 33.0 | 8.4 (6.8–10.4) | 1.84 ± 0.67 | 0.09 (0.07–0.11) |
| Cloral (l/min) | 1.73 ± 0.7 | 0.62 ± 0.38 | 0.31 (0.18–0.52) | 0.18 ± 0.04 | 0.12 (0.10–0.15) | 20.3 ± 7.1 | 11.7 (9.3–14.8) |
| Cloral (ml · min−1 · kg−1) | 24.7 ± 11.5 | 8.41 ± 6.44 | 0.31 (0.18–0.52) | 2.43 ± 0.55 | 0.12 (0.10–0.15) | 265 ± 94.4 | 11.7 (9.3–14.8) |
| Clformation (l/min) | 1.14 ± 0.5 | 0.40 ± 0.27 | 0.27 (0.15–0.50) | 0.10 ± 0.05 | 0.10 (0.07–0.14) | 9.8 ± 3.8 | 8.3 (6.4–10.8) |
| t1/2 (h) | 3.8 ± 1.5 | 4.4 ± 1.5 | 1.1 (0.90–1.4) | 11.4 ± 3.8 | 3.2 (2.6–3.9) | 0.97 ± 0.30 | 0.27 (0.22–0.32) |
| Intravenous | |||||||
| AUC0–∞ (h · ng/ml) | 36.2 ± 10.4 | 66.3 ± 22.0 | 2.0 (1.7–2.4) | 120 ± 23.6 | 3.0 (2.7–3.4) | 16.1 ± 2.9 | 0.48 (0.43–0.54) |
| Cli.v. (l/min) | 0.49 ± 0.11 | 0.28 ± 0.09 | 0.51 (0.42–0.61) | 0.14 ± 0.03 | 0.33 (0.30–0.37) | 1.06 ± 0.17 | 2.1 (1.8–2.3) |
| Cli.v. (ml · min−1 · kg−1) | 6.68 ± 1.62 | 3.51 ± 1.17 | 0.51 (0.42–0.61) | 1.92 ± 0.56 | 0.33 (0.30–0.37) | 13.9 ± 2.32 | 2.1 (1.8–2.3) |
| Clformation (l/min) | 0.34 ± 0.08 | 0.16 ± 0.08 | 0.41 (0.29–0.56) | 0.05 ± 0.02 | 0.19 (0.16–0.22) | 0.68 ± 0.10 | 1.9 (1.7–2.1) |
| t1/2 (h) | 4.1 ± 1.5 | 5.8 ± 4.2 | 1.2 (0.89–1.7) | 11.7 ± 6.3 | 2.7 (2.5–3.0) | 2.5 ± 1.1 | 0.65 (0.57–0.73) |
| F | 0.31 ± 0.09 | 0.61 ± 0.24 | 1.7 (0.97–2.9) | 0.79 ± 0.13 | 2.8 (2.3–3.3) | 0.06 ± 0.02 | 0.18 (0.15–0.23) |
| FH | 0.43 ± 0.15 | 0.69 ± 0.10 | 1.8 (1.5–2.1) | 0.83 ± 0.05 | 1.8 (1.5–2.2) | N.A.a | |
| FA · FG | 0.78 ± 0.25 | 0.89 ± 0.37 | 0.96 (0.60–1.5) | 0.96 ± 0.20 | 1.5 (1.4–1.7) | N.A. | |
| Hepatic Clint fold change (fClintHep) | 0.24 ± 0.11 | 0.21 (0.13–0.34) | 0.12 ± 0.09 | 0.10 (0.06–0.17) | N.A. | ||
| GI Clint fold change (fClintGI) | 0.38 ± 1.4 | 0.55 (0.07–6.8) | −0.04 ± 0.45 | 0.22 (0.10–0.48) | N.A. | ||
↵a N.A., not available. FH, FA · FG, fClintGI, and fClintHep are not available for MDZ after RIF treatment because of intravenous blood clearance exceeding the estimated hepatic blood flow. All reported clearance values are plasma clearances.