Table 1.
Median (95% CI) ratio of predicted pharmacokinetic parameters of the scenario with IL‐6 divided by the scenario without IL‐6 for lopinavir/ritonavir 400/100 mg twice daily and midazolam 5 mg as a single dose
| IL‐6 [pg/mL] | Cmax | Tmax | AUCt | CLF | VdF | t1/2 |
|---|---|---|---|---|---|---|
| Lopinavir/ritonavir | ||||||
| 1 | 1.67 (1.32; 2.24) | 1.13 (1.06; 1.22) | 2.22 (1.56; 2.76) | 0.45 (0.36; 0.64) | 0.98 (0.85; 4.22) | 2.28 (1.40; 9.06) |
| 5 | 1.72 (1.30; 2.43) | 1.15 (1.06; 3.28) | 2.28 (1.50; 3.08) | 0.44 (0.32; 0.67) | 1.02 (0.83; 4.89) | 2.37 (1.36; 11.05) |
| 10 | 1.77 (1.31; 2.38) | 1.13 (1.08; 1.27) | 2.31 (1.58; 2.98) | 0.43 (0.34; 0.63) | 1.07 (0.87; 7.50) | 2.53 (1.42; 16.98) |
| 50 | 1.78 (1.28; 2.31) | 1.14 (1.06; 1.44) | 2.32 (1.48; 2.91) | 0.43 (0.34; 0.67) | 1.04 (0.85; 8.73) | 2.49 (1.27; 20.71) |
| 100 | 1.70 (1.35; 2.30) | 1.13 (1.06; 1.25) | 2.23 (1.66; 2.96) | 0.45 (0.34; 0.60) | 0.99 (0.84; 8.89) | 2.28 (1.42; 18.24) |
| 500 | 1.75 (1.35; 2.36) | 1.13 (1.07; 1.25) | 2.34 (1.62; 2.95) | 0.43 (0.34; 0.62) | 1.01 (0.85; 3.34) | 2.40 (1.45; 9.66) |
| 1,000 | 1.73 (1.27; 2.41) | 1.13 (1.05; 2.34) | 2.21 (1.33; 3.08) | 0.45 (0.32; 0.75) | 0.99 (0.77; 10.61) | 2.30 (1.09; 29.76) |
| 5,000 | 1.75 (1.36; 2.31) | 1.13 (1.07; 1.25) | 2.29 (1.73; 2.93) | 0.44 (0.34; 0.58) | 1.01 (0.85; 11.29) | 2.41 (1.49; 27.11) |
| 10,000 | 1.76 (1.31; 2.28) | 1.14 (1.07; 1.39) | 2.26 (1.58; 2.92) | 0.44 (0.34; 0.63) | 1.04 (0.88; 7.82) | 2.47 (1.49; 16.69) |
| 50,000 | 1.74 (1.32; 2.29) | 1.13 (1.07; 2.25) | 2.35 (1.62; 2.99) | 0.43 (0.33; 0.62) | 1.00 (0.84; 3.28) | 2.38 (0.62; 35.67) |
| Cmax | Tmax | AUCt | CLF | VdF | t1/2 |
|---|---|---|---|---|---|
| Midazolam | |||||
| 1.10 (1.04; 1.18) | 1.00 (1.00; 1.33) | 1.22 (1.08; 1.43) | 0.82 (0.70; 0.93) | 0.89 (0.82; 0.96) | 1.08 (1.02; 1.21) |
| 1.10 (1.05; 1.18) | 1.00 (1.00; 1.33) | 1.21 (1.09; 1.52) | 0.82 (0.66; 0.92) | 0.89 (0.83; 0.95) | 1.07 (1.03; 1.29) |
| 1.10 (1.05; 1.19) | 1.00 (1.00; 1.33) | 1.21 (1.09; 1.52) | 0.82 (0.66; 0.92) | 0.89 (0.83; 0.95) | 1.07 (1.03; 1.29) |
| 1.10 (1.04; 1.18) | 1.00 (1.00; 1.33) | 1.21 (1.08; 1.43) | 0.83 (0.70; 0.92) | 0.89 (0.82; 0.95) | 1.07 (1.03; 1.27) |
| 1.10 (1.04; 1.18) | 1.00 (1.00; 1.33) | 1.21 (1.08; 1.44) | 0.82 (0.70; 0.92) | 0.89 (0.82; 0.95) | 1.07 (1.03; 1.27) |
| 1.10 (1.02; 1.18) | 1.00 (1.00; 1.33) | 1.19 (1.06; 1.49) | 0.84 (0.67; 0.94) | 0.90 (0.83; 0.97) | 1.07 (1.02; 1.28) |
| 1.10 (1.03; 1.19) | 1.00 (1.00; 1.33) | 1.20 (1.06; 1.50) | 0.83 (0.67; 0.94) | 0.90 (0.82; 0.96) | 1.07 (1.02; 1.30) |
| 1.13 (1.05; 1.21) | 1.00 (1.00; 1.33) | 1.27 (1.09; 1.56) | 0.79 (0.64; 0.91) | 0.87 (0.79; 0.95) | 1.09 (1.03; 1.29) |
| 1.13 (1.05; 1.24) | 1.00 (1.00; 1.33) | 1.29 (1.10; 1.66) | 0.78 (0.60; 0.91) | 0.86 (0.77; 0.95) | 1.10 (1.03; 1.31) |
| 1.16 (1.06; 1.27) | 1.00 (1.00; 1.33) | 1.33 (1.12; 1.83) | 0.75 (0.55; 0.89) | 0.85 (0.75; 0.94) | 1.12 (1.04; 1.47) |
AUCt, area under the curve over time; CI, confidence interval; CLF, clearance; Cmax, peak concentration; t1/2, elimination half‐life; VdF, volume of distribution.