TABLE 1.
Summary of prespecified and post hoc budesonide PK parameters (PK analysis set) after an oral dose of BOS (low or high dose)
| Parameter | Low-dose BOS | High-dose BOS | Ratio of geometric LS means (90% CI) for high- vs low-dose BOS | |||
|---|---|---|---|---|---|---|
| 0.35 mg | 0.5 mg | 1.4 mg | 2.0 mg | 2–9 | 10–18 | |
| (2–9 years old) | (10–18 years old) | (2–9 years old) | (10–18 years old) | years old | years old | |
| (n = 4) | (n = 5) | (n = 15) | (n = 13) | |||
| AUC0–last, hour×pg/mL | ||||||
| Mean | 1139.5 | 743.8 | 3259.3 | 3636.9 | ||
| SD | 800.8 | 425.3 | 2109.4 | 1769.9 | ||
| Geometric LS mean | 903.9 | 654.5 | 2636.4 | 3282.7 | 2.92 (1.4–6.2) | 5.02 (3.2–7.9) |
| 95% CI | 401.8–2033.4 | 410.9–1042.6 | 1734.6–4007.1 | 2459.5–4381.5 | ||
| Median | 1026.0 | 551.0 | 2580.0 | 2700.0 | ||
| Min, max | 286, 2220 | 328, 1390 | 320, 8270 | 1730, 7240 | ||
| AUC0–tau, hour×pg/mL* | ||||||
| Mean | 1710 | 1270 | 4260 | 4840 | ||
| SD | 846 | 713 | 2380 | 2580 | ||
| Median | 1780 | 1050 | 3150 | 3640 | ||
| Min, max | 613, 2670 | 726, 2230 | 1750, 10,100 | 2460, 10,100 | ||
| Cmax, pg/mL | ||||||
| Mean | 492.0 | 195.0 | 1019.5 | 958.4 | ||
| SD | 417.8 | 64.4 | 670.2 | 527.6 | ||
| Geometric LS mean | 355.2 | 187.2 | 805.2 | 841.1 | 2.27 (1.0–5.2) | 4.49 (2.9–7.0) |
| 95% CI | 143.9–877.0 | 118.4–296.1 | 504.9–1284.0 | 633.0–1117.7 | ||
| Median | 402.0 | 191.0 | 812.0 | 708.0 | ||
| Min, max | 104, 1060 | 139, 296 | 70, 2550 | 359, 2210 | ||
| Tmax, hour | ||||||
| Mean | 0.7 | 1.2 | 0.9 | 1.1 | ||
| SD | 0.4 | 0.4 | 0.4 | 0.5 | ||
| Median | 0.5 | 1.0 | 1.0 | 1.0 | ||
| Min, max | 0.5, 1.2 | 1, 2 | 0.5, 2 | 0.5, 2 | ||
| T1/2, hour | ||||||
| Mean | 3.3 | 3.4 | 3.5 | 3.5 | ||
| SD | 0.8 | 0.8 | 2.7 | 1.0 | ||
| Median | 3.2 | 3.5 | 2.7 | 3.6 | ||
| Min, max | 2.4, 4.4 | 2.3, 4.2 | 1.9, 12.7 | 2.1, 5.1 | ||
| CL/F, L/hour* | ||||||
| Mean | 274 | 491 | 417 | 516 | ||
| SD | 200 | 235 | 192 | 219 | ||
| Median | 198 | 525 | 446 | 550 | ||
| Min, max | 131, 571 | 224, 689 | 139, 800 | 199, 814 | ||
| VZ/F, L* | ||||||
| Mean | 1300 | 2240 | 1860 | 2570 | ||
| SD | 888 | 856 | 1220 | 1200 | ||
| Median | 1110 | 2110 | 1760 | 2660 | ||
| Min, max | 447, 2520 | 1360, 3380 | 496, 5490 | 1030, 4460 | ||
AUC0–last = area under the plasma concentration-time curve from time zero (T0) to the last quantifiable concentration; AUC0–tau = area under the plasma concentration-time curve during a dosing interval, where tau is 12 hours for twice-daily BOS dosing and 24 hours for once-daily BOS dosing; BOS = budesonide oral suspension; CI = confidence interval; CL/F = apparent oral clearance; Cmax = maximum observed plasma concentration; LS = least-squares; max = maximum; min = minimum; PK = pharmacokinetic; SD = standard deviation; T1/2 = terminal elimination half-life; Tmax = time to Cmax; VZ/F = apparent volume of distribution associated with the terminal slope.
0.5 mg, n = 4; 1.4 mg, n = 14.