Table 3.
Secondary pharmacokinetic parameters of miltefosine in Eastern African patients with VL treated with either miltefosine monotherapy or combination therapy
| Secondary parametera [median (range)] |
|||||
|---|---|---|---|---|---|
| Monotherapy (28 days miltefosine) | Total (n = 48) | Paediatricb (n = 19) | Adultb (n = 29) | Diff (%)c | P value |
| Initial half-life (days) | 7.05 (4.02–10.9) | 7.02 (4.02–8.45) | 7.18 (5.35–10.9) | –2 | 0.258 |
| Terminal half-life (days) | 79.4 (49.9–103) | 77.8 (54.9–95.6) | 81.3 (49.9–103) | –4 | 0.073 |
| AUC0–∞ (μg·day/mL) | 713 (237–1482) | 545 (314–1080) | 812 (237–1482) | –33 | 0.006d |
| AUC0–28d (μg·day/mL) | 423 (191–767) | 352 (232–593) | 497 (191–767) | –29 | 0.002d |
| Time > EC50 (days) | 51.4 (30.5–77.1) | 48.3 (36.3–62.4) | 52.9 (30.5–77.1) | –9 | 0.024e |
| Time > EC90 (days) | 27.0 (4.29–43.8) | 22.1 (11.0–34.2) | 27.8 (4.29–43.8) | –21 | 0.005d |
| Combination therapy (10 days miltefosine) | Total (n = 47) | Paediatricb (n = 22) | Adultb (n = 25) | Diff (%)c | P value |
| Initial half-life (days) | 7.39 (5.41–10.3) | 6.76 (5.58–9.00) | 7.52 (5.41–10.3) | –12 | 0.031e |
| Terminal half-life (days) | 78.5 (62.4–98.6) | 76.7 (66.0–98.6) | 79.7 (62.4–93.7) | –4 | 0.231 |
| AUC0–∞ (μg·day/mL) | 290 (70.1–496) | 197 (136–496) | 313 (70.1–483) | –37 | 0.004d |
| AUC0–10 (μg·day/mL) | 87.9 (31.1–136) | 69.5 (31.1–129) | 95.9 (32.3–136) | –28 | 0.004d |
| Time > EC50 (days) | 31.2 (14.2–46.9) | 28.5 (23.1–43.0) | 34.1 (14.2–46.9) | –16 | 0.013e |
| Time > EC90 (days) | 8.98 (0–16.8) | 3.17 (0–16.8) | 9.93 (0–16.2) | –68 | 0.002d |
a
Time > EC50, time the miltefosine concentration was above the in vitro susceptibility value EC50; Time > EC90, time the miltefosine concentration was above the in vitro susceptibility value EC90; P value, calculated based on Mann–Whitney U-test.
b
Paediatric defined as having an age <12 years and adult defined as having an age ≥12 years.
c
Percentage difference between the median adult and paediatric ([paediatric – adult]/adult) pharmacokinetic parameter.
d
Below significance level of P < 0.01.
e
Below significance level of P < 0.05.