Table 3.
Within-children pharmacokinetic substudy in 26 children randomized to once-daily arm.
| (a) Baseline characteristics | ||||
| Weight band | ||||
| ≥15 to ≤25 kg | >25 to ≤35 kg | >35 kg | Total | |
| Children: n | 7 | 8 | 11 | 26 |
| Men: n (%) | 4 (57) | 5 (63) | 3 (27) | 12 (46) |
| Age (years): median (IQR) [range] | 7.1 (6.7, 8.7) [4.4, 8.9] | 10.6 (9.5, 15.0) [6.3, 16.0] | 14.3 (13.5, 15.4) [12.7, 16.8] | 12.8 (8.7, 14.7) [4.4, 16.8] |
| Weight (kg): median (IQR) [range] | 19.4 (19.0, 23.1) [15.0, 24.1] | 30.7 (29.8, 32.1) [26.4, 33.8] | 42.0 (38.5, 49.5) [36.0, 72.5] | 32.1 (24.1, 41.0) [15.0, 72.5] |
| BMI (kg/m2): median (IQR) [range] | 15.1 (14.4, 15.7) [11.5,15.8] | 15.7 (14.8, 18.0) [14.5, 19.4] | 17.7 (17.4, 20.6) [16.0, 27.6] | 16.5 (15.1, 18.6) [11.5, 27.6] |
| Vertically infected: n (%) | 7 (100) | 8 (100) | 11 (100) | 26 (100) |
| Ethnic origin: n (%) | ||||
| White | 0 (0) | 1 (13) | 1 (9) | 2 (8) |
| Black: African or other | 2 (29) | 3 (38) | 2 (18) | 7 (27) |
| Mixed black/white | 1 (14) | 1 (13) | 0 (0) | 2 (8) |
| Asian/Thai | 4 (57) | 3 (38) | 7 (64) | 14 (54) |
| Other | 0 (0) | 0 (0) | 1 (9) | 1 (4) |
| (b) Pharmacokinetic parameters for lopinavir on once-daily (week 4) and twice-daily (week 0) dosing | ||||
| n | Once-daily geometric mean (95% CI)c | Twice-daily geometric mean (95% CI)c | Once-daily/twice-daily geometric mean ratio (90% CI) | |
| AUC0–24 (h*mg/l)a | ||||
| Total: | 26 | 160.9 (138.4, 187.0) | 223.9 (194.8, 257.4) | 0.72 (0.62, 0.83) |
| Weight: | ||||
| ≥15 to ≤25 kg | 7 | 172.6 (121.3, 245.7) | 232.1 (153.3, 351.4) | |
| >25 to ≤35 kg | 8 | 159.3 (120.6, 210.5) | 256.8 (209.3, 315.2) | |
| >35 kg | 11 | 155.0 (116.8, 205.6) | 198.1 (159.8, 245.5) | |
| Cmax (mg/l) | ||||
| Total: | 26 | 14.0 (12.7, 15.6) | 12.5 (11.1, 14.0) | 1.13 (1.00, 1.26) |
| Weight: | ||||
| ≥15 to ≤25 kg | 7 | 15.5 (12.4, 19.4) | 13.5 (9.8, 18.7) | |
| >25 to ≤35 kg | 8 | 15.0 (12.2, 18.5) | 14.1 (11.4, 17.3) | |
| >35 kg | 11 | 12.5 (10.7, 14.7) | 10.9 (9.3, 12.6) | |
| Clast (mg/l) | ||||
| Total: | 26 | 1.03 (0.61, 1.75) | 5.69 (4.58, 7.07) | 0.18 (0.12, 0.27) |
| Weight: | ||||
| ≥15 to ≤25 kg | 7 | 0.91 (0.27, 3.07) | 4.92 (2.65, 9.16) | |
| >25 to ≤35 kg | 8 | 0.93 (0.38, 2.26) | 6.65 (5.22, 8.47) | |
| >35 kg | 11 | 1.20 (0.42, 3.44) | 5.57 (3.73, 8.32) | |
| Clearance (l/(h*kg))b | ||||
| Total: | 26 | 0.115 (0.099, 0.134) | 0.084 (0.074, 0.095) | 1.37 (1.19, 1.57) |
| Weight: | ||||
| ≥15 to ≤25 kg | 7 | 0.112 (0.076, 0.165) | 0.085 (0.062, 0.117) | |
| >25 to ≤35 kg | 8 | 0.120 (0.091, 0.158) | 0.076 (0.062, 0.094) | |
| >35 kg | 11 | 0.114 (0.086, 0.150) | 0.089 (0.071, 0.113) | |
| Tmax(h)c | ||||
| Total: | 26 | 4.0 (2.0, 8.0) | 3.5 (0.0, 12.0) | |
| Weight: | ||||
| ≥15 to ≤25 kg | 7 | 4.0 (2.0, 8.0) | 3.8 (0.0, 4.1) | |
| >25 to ≤35 kg | 8 | 4.0 (2.0, 6.0) | 2.8 (1.7, 4.0) | |
| >35 kg | 11 | 4.0 (2.0, 8.0) | 3.4 (1.7, 12.0) | |
aAUC0–24 for b.i.d. dosing = AUC0–12*2.
bClearance calculated as Cl/F/kg = dose(mg)/[AUC0–24(h*mg/l)*body weight (kg)].
cFor Tmax median values (minimum, maximum) are reported.