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. 2019 Dec 26;6(2):173–179. doi: 10.1021/acsinfecdis.9b00396

Table 2. In Vivo Efficacy and Terminal Plasma Concentrations of 8a and Flubendazolea.

          drug concentration (μM)
in vivo model drug treatment worm count median ± SEM (range) adult worm reduction/animals with no worms P ≤ 24 h after last dose interim necropsy
B. malayi; necropsy on day 42 vehicle (SC study), n = 5 12 ± 0.73 (11–15)     N/A N/A N/A
flubendazole, 10 mg/kg × 5 days, QD, SC, n = 10 0 ± 0 (0–0) 100%/100% 0.0001 0.173 NM 0.043
8a, 150 mg/kg × 14 days, QD, SC (solution), n = 6 2 ± 2.14 (0–12) 83.3%/50% 0.0622 2.47 0.07 (day 28) 0.01
8a, 100 mg/kg × 14 days, QD, SC (suspension), n = 16 0 ± 0.19 (0–3) 100%/87.5% 0.0001 4.10 5.36 (day 28) 3.38
vehicle (PO study), n = 5 8 ± 0.81 (5–10)     N/A N/A N/A
8a, 100 mg/kg × 28 days, QD, PO (suspension), n = 10 7 ± 1.38 (4–16) 12.5%/0% 0.9999 0.128 NM <LOQ
B. pahangi; necropsy on day 63; n = 5 per group vehicle 89 ± 12.79 (64–146)     N/A N/A N/A
flubendazole, 10 mg/kg × 5 days, QD, SC 0 ± 0 (0–0) 100%/100% 0.0009 0.178 NM 0.018
8a, 100 mg/kg × 14 days, QD, SC (suspension) 0 ± 0.333 (0–2) 100%/83% 0.0024 5.87 NM 1.15
8a, 100 mg/kg × 28 days, QD, PO (suspension) 67.5 ± 14.86 (2–114) 24%/0% 0.9999 0.13 NM <LOQ
L. sigmodontis; necropsy on day 63; n = 4 vehicle; n = 6 other groups vehicle 8.5 ± 3.28 (5–20)     N/A   N/A
flubendazole, 10 mg/kg × 5 days, QD, SC 0 ± 0 (0–0) 100%/100% 0.0208 0.283 NM 0.040
8a, 100 mg/kg × 14 days, QD, SC (suspension) 0 ± 0.34 (0–2) 100%/33.3% 0.1207 9.30 NM 0.069
8a, 300 mg/kg × 7 days, QD, SC (suspension) 0 ± 0 (0–0) 100%/100% 0.0208 7.85 10.6 (day 21) 0.48
4.64 (day 42)
8a, 100 mg/kg × 28 days, QD, PO (suspension) 20 ± 6.92 (5–50) –135.3%/0% 0.999 0.210 0.006 (day 42) 0.003
a

NM = not measured. N/A = not applicable. Statistical significance was tested by Kruskal–Wallis followed by Dunn’s multiple comparisons test.