Pharmacokinetics of ivermectin metabolites and their activity against Anopheles stephensi mosquitoes

Malaria Journal

Table 1 Pharmacokinetic parameters of ivermectin metabolites in whole blood for 12 subjects after a dose of 12 mg ivermectin

Ivermectin metabolite	T_max [h]	C_max [ratio]	Half-life [h]	MRT_last [h]
M1	7.0 ± 0.5	0.011 ± 0.001	54.2 ± 4.7	33.8 ± 0.9
M2	6.3 ± 0.3	0.010 ± 0.0010	31.9 ± 3.4	25.8 ± 0.7
M3	5.3 ± 0.2	0.003 ± 0.0003	15.9 ± 2.8	13.9 ± 1.3
M4	6.0 ± 0.2	0.004 ± 0.0004	57.5 ± 13.2	29.4 ± 1.7
M5	6.4 ± 0.4	N/A	N/A	N/A
M6	5.4 ± 0.4	0.002 ± 0.0002	32.4 ± 4.1	18.3 ± 1.6
M7	6.1 ± 0.4	N/A	N/A	N/A
M8	5.0 ± 0.3	N/A	N/A	N/A
M9	6.0 ± 0.8	N/A	N/A	N/A

Parent	T_max [h]	C_max [ng/mL]	Half-life [h]
Ivermectin*	4.4 ± 1.4	70.7 ± 16.1	38.9 ± 20.8

Blood was collected on volunteers pre- and up to 72 h post-ivermectin dose (Duthaler et al., 2019) [25]. Non-compartmental analysis (NCA) was used to derive the ivermectin metabolites pharmacokinetic parameters. Pharmacokinetic parameters are showed as mean (± SE). The ratio area/internal standard area was used for the metabolites, whereas ivermectin quantitative data with SD was taken in plasma (*) from [25] . The least abundant metabolites M5, M7, M8 and M9 were excluded from the NCA analysis. Abbreviations: standard error (SE); time of peak concentration (T_max); peak concentration (C_max); Mean residence time from the time of dosing to the time of the last measurable concentration for a substance administered by extravascular dosing (MRT_last)

ISSN: 1475-2875