Ivermectin as a potential COVID-19 treatment from the pharmacokinetic point of view: antiviral levels are not likely attainable with known dosing regimens

Figures & data

Table 1. Published pharmacokinetic parameters for ivermectin following clinically relevant and excessive dosing.

Pharmacokinetic study	Dose	Absorption parameters				Elimination
		Cmax (ng/mL)	Cmax (nmol/L)	tmax (h)	t1/2(abs) (h)	t½ (h)	Cl (1 kg^−1·day^−1)
Krishna et al., 1993 [17]	6 mg (tablets)	23.1	26.4	4.3	0.5	12.6	4.28
Krishna et al., 1993 [17]	12 mg (tablets)	30.4	34.7	10.3	2.5	13.4	4.03
Long et al., 2001 [18]	6 mg (tablets)	20.2	23.1	4.7	1.4	11.1	7.57
Long et al., 2001 [18]	12 mg (tablets)	23.5	26.9	5.3	1.4	21.1	6.53
Long et al., 2001 [18]	18 mg (tablets)	31.2	35.7	5.1	1.7	16.7	10.6
Edwards et al., 1988 [19]	12 mg (solution)	81	92.6	3.6	–	–	–
Edwards et al., 1988 [19]	12 mg (tablets)	50	57.1	3.4	–	–	–
Edwards et al., 1988 [19]	12 mg (capsules)	46	52.6	3.6	–	–	–
Ogbuokiri et al., 1993 [20]	150 μg/kg	37.9	43.3	–	–	–	–
Baraka et al.,1996 [21]	150 μg/kg	52.2	59.7	5.2	–	35.0	–
Elkassaby, 1991 [22]	150 μg/kg	39	44.6	5.6	–	16	–
Okonkwo, et al., 1993 [23]	6 mg (tablets)	38.2	43.7	4.7	–	54.5	3.1
Njoo, et al. 1995 [24]	150 μg/kg	–	–	–	–	19.9	–
Muñoz, et al., 2018 [25]	36 mg (550–700 μg/kg)	96.2	109.9	3.64	–	91.77
Guzzo et al., 2002 [12]	90 mg	158.1	180.7	4.9	–	18.8	–
Guzzo et al., 2002 [12]	120 mg (1404–2000 µg/kg)	247.8	283.2	4.2	–	19.1	–

Table 2. Comparison between the in vitro inhibitory concentration of ivermectin [11] with exemplar published C_max values of the drug [1, 127].

In vitro end-points [11]	Inhibitory concentrations (µmol/L)	Inhibitory concentrations recalculated in µg/mL	Inhibitory concentrations recalculated in ng/mL	Ratio between the inhibitory concentrations and clinically relevant Cmax (96.2 ng/mL)	Ratio between the inhibitory concentrations and Cmax after excessive dosing 247.8 (ng/mL)
IC50 – cell associated (E gene)*	2.8	2.45	2450	25.5	9.9
IC50 – supernatant (E gene)	2.4	2.1	2100	25.9	8.5
IC50 – cell associated (RdRp gene)**	2.5	2.19	2190	27.0	8.8
IC50 – supernatant (RdRp gene)	2.2	1.95	1950	24.1	7.9
Average IC50	2.475	2.166	2166	22.51	8.74
IC90–100 (highest and most effective concentration tested)	5.0	4.3755	4375	55.0	17.7

* E – envelope protein gene.

** RdRp – RNA-dependent-RNA-polymerase gene [11].

The data values have been bolded as they represent the ratios between the average IC₅₀ and te IC₉₀ endpoints and the C_max values.

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