Translation of liver stage activity of M5717, a Plasmodium elongation factor 2 inhibitor: from bench to bedside

Malaria Journal

Table 1 In vivo average blood concentration of M5717 over 24 h

Dose in mg/kg	Cure^a	Mean whole blood concentration in ng/mL at 2 h (n = 3)	SD	Mean whole blood Concentration in ng/mL at 24 h (n = 3)	SD	AUC_{0 − 24 h} in ng/mL.h (n = 3)	Cav_{0 − 24 h}^b in nM (n = 3)	Cav_{0 − 24 h}^b/IC₉₉ ratio
0.3	0/5^c	7.36	0.63	4.91	0.55	142.33	3.6	0.4
0.6	1/2	–	–	–	–	–	–	~ 1^d
1.5	2/2	–	–	–	–	–	–	~ 2^d
3	3/3	84.83	25.03	41.97	9.73	1479.63	37.9	4
30	3/3	1058	301.48	576.3	169.01	19035.3	487.1	49

^aBased on a > 30-day follow-up of blood stage parasitaemia. Atovaquone (10 mg/kg) was used as a positive control in these experiments
^bCorrection was made for Blood/Plasma ratio (mouse B/P = 3.52) as only the plasma concentrations are able to interact with the parasites. No plasma protein correction was made here as both in vitro and in vivo contained proteins at high levels
^cPooled batches
^dEstimation based on observed dose linearity across doses tested. A noncompartmental analysis was performed to determine the AUC_0−24 h using the Phoenix WinNonlin program (version 6.3)

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