TABLE 3.
Summary of PK parameters
| 50 g mannitol (N = 15) | 100 g mannitol (N = 11) | 150 g mannitol (N = 16) | |
|---|---|---|---|
| C max (mg/ml) | |||
| n | 15 | 11 | 16 |
| Mean (SD) | 0.630 (0.145) | 1.024 (0.279) | 1.359 (0.391) |
| 95% CI | 0.550; 0.711 | 0.836; 1.211 | 1.150; 1.567 |
| Median | 0.644 | 0.944 | 1.510 |
| Q1; Q3 | 0.505; 0.702 | 0.850; 1.219 | 1.031; 1.695 |
| Min; max | 0.402; 0.951 | 0.532; 1.617 | 0.716; 1.798 |
| T max (h) | |||
| n | 15 | 11 | 16 |
| Median | 1.000 | 1.000 | 1.000 |
| Q1; Q3 | 0.920; 1.000 | 1.000; 2.000 | 1.000; 1.920 |
| Min; max | 0.920; 2.000 | 0.920; 2.080 | 0.920; 2.030 |
| AUC0−t8 (mg/ml*h) | |||
| n | 15 | 11 | 16 |
| Mean (SD) | 2.231 (0.521) | 4.159 (1.348) | 5.590 (2.181) |
| 95% CI | 1.943; 2.520 | 3.253; 5.065 | 4.428; 6.752 |
| Median | 2.130 | 4.390 | 6.065 |
| Q1; Q3 | 1.830; 2.690 | 2.890; 5.300 | 3.515; 7.420 |
| Min; max | 1.300; 3.160 | 2.010; 6.360 | 2.270; 8.570 |
| AUC 0−∞ (mg/ml*h) | |||
| n | 15 | 11 | 16 |
| Mean (SD) | 2.667 (0.668) | 4.992 (1.706) | 7.403 (3.472) |
| 95% CI | 2.297; 3.037 | 3.846; 6.139 | 5.618; 9.189 |
| Median | 2.515 | 5.421 | 7.928 |
| Q1; Q3 | 2.161; 3.241 | 3.384; 6.560 | 4.434; 9.715 |
| Min; max | 1.523; 4.020 | 2.270; 7.560 | 2.650; 15.751 |
| t 1/2 (h) | |||
| n a | 13 | 7 | 11 |
| Mean (SD) | 2.584 (0.840) | 2.419 (0.579) | 2.678 (0.489) |
| 95% CI | 2.076; 3.091 | 1.883; 2.954 | 2.350; 3.007 |
| Median | 2.470 | 2.320 | 2.600 |
| Q1; Q3 | 2.070; 2.530 | 1.990; 2.850 | 2.260; 3.240 |
| t 1/2 (h) | |||
| Min; max | 1.840; 4.690 | 1.800; 3.480 | 2.010; 3.370 |
| Bioavailability b | |||
| n | 15 | 11 | 16 |
| Mean (SD) | 0.243 (0.073) | 0.209 (0.081) | 0.228 (0.093) |
| 95% CI | 0.202; 0.283 | 0.154; 0.264 | 0.180; 0.276 |
| Median | 0.230 | 0.197 | 0.229 |
| Q1; Q3 | 0.209; 0.254 | 0.129; 0.286 | 0.169; 0.294 |
| Min; max | 0.144; 0.435 | 0.103; 0.326 | 0.095; 0.391 |
Abbreviations: AUC 0−∞ , area under concentration–time curve T 0−∞ ; AUC0−t , area under concentration–time curve T 0–T 8; CI, confidence interval; C max, maximum concentration; PK, pharmacokinetic; Q1, first quartile; Q3, third quartile; SD, standard deviation; t 1/2, terminal elimination half‐life; T max, time to reach maximum concentration.
Only 31 patients of the 42 patients in the PK population (13, 7 and 11 patients in the 50, 100, and 150 g dose groups, respectively) satisfied all punctual sampling for the calculation of mannitol t ½.
Bioavailability has been calculated by dividing the AUC0−∞ corrected for the patients’ average body weight by the AUC0−∞ after i.v. administration of mannitol 1 g/kg body weight, as reported by Rudehill et al. 18