Table 6.

Binding to plasma and media proteins

Compound	Fraction unbound ± SD
	Human Plasmaa	Albumaxa	10% FCS in DMEMa	HLMa
Ionized or partially ionized bases at physiological pH
Cycloguanil	0.75 ± 0.040	0.88 ± 0.057	0.94 ± 0.064	0.72 ± 0.083
Doxycyclin	0.23 ± 0.090b	0.41 ± 0.023	0.44 ± 0.070	0.93 ± 0.045
Pyronaridine	0.090 ± 0.012b	0.69 ± 0.023	Not assessed	0.29 ± 0.018
Proguanil	0.34 ± 0.010	0.80 ± 0.021	Not assessed	0.33 ± 0.014
Primaquine	0.26 ± 0.023	0.96 ± 0.056	0.78 ± 0.025	0.56 ± 0.050
Chloroquine	0.54 ± 0.048	0.97 ± 0.069	Not assessed	0.50 ± 0.032
Chlorproguanil	0.10 ± 0.0070	0.50 ± 0.020	Not assessed	0.052 ± 0.004
Azithromycin	0.34, 0.35b	0.76 ± 0.065	Not assessed	0.70 ± 0.060
AQ-13	0.43 ± 0.022	0.85 ± 0.028	Not assessed	0.66 ± 0.048
Desethylamodiaquine	0.17 ± 0.0020	0.75 ± 0.074	Not assessed	not assessed
Quinine	0.37 ± 0.040b	0.69 ± 0.090	Not assessed	0.57 ± 0.036
Clindamycin	0.19 ± 0.011	0.65 ± 0.066	Not assessed	0.67 ± 0.084
KAF156	0.069 ± 0.013b	0.38 ± 0.017	0.477 ± 0.032	0.14 ± 0.0060
M5717	0.24 ± 0.0020b	0.55 ± 0.041	0.638 ± 0.065	0.50 ± 0.041
OZ277	0.086 ± 0.0080	0.29 ± 0.021	Not assessed	0.044 ± 0.0050
Mefloquine	0.015 ± 0.0010b	0.27 ± 0.019	Not assessed	0.050 ± 0.0060
Amodiaquine	0.089 ± 0.0080	0.67 ± 0.033	Not assessed	0.91 ± 0.094
NPC1161B	0.00074 ± 0.00016c	0.035 ± 0.0020	0.043 ± 0.004	CNDe
Ferroquine	0.041 ± 0.0010c	0.52 ± 0.031	0.364 ± 0.026	0.27 ± 0.032
Naphthoquine	0.018 ± 0.0010c	0.27 ± 0.035	Not assessed	0.21 ± 0.015
Tafenoquine	0.00070 ± 0.00017c	CNDe	0.038 ± 0.001	0.0020 ± 0.00030
MMV253	0.017 ± 0.00020c	0.48 ± 0.026	Not assessed	0.11 ± 0.017
MMV052	0.00040 ± 0.00010c	0.014 ± 0.0010	Not assessed	0.0010 ± 0.00010
Piperaquine	0.0003 ± 0.0001c	0.019 ± 0.0040	0.092 ± 0.0030	0.013 ± 0.0020
Halofantrine	< 0.0001c	0.0080 ± 0.0010	Not assessed	0.0020 ± 0.00020
TDD-E209	< 0.0001c	0.0070 ± 0.0010	Not assessed	0.00030 ± 0.000010
Lumefantrine	< 0.0001c	CNDe	Not assessed	CNDe
Ionized acids at physiological pH
Sulfadoxine	0.036 ± 0.0010	0.50 ± 0.030	0.86 ± 0.044	0.93 ± 0.086
Sulfamethoxazole	0.32 ± 0.024	0.67 ± 0.120	0.87 ± 0.058	1.00 ± 0.033
Artesunate	0.27 ± 0.0080d	0.14 ± 0.0070d	0.72 ± 0.026	CNDd
Atovaquone	< 0.0001c	CNDe	CNDe	~ 0.0020
Zwitterionic or partially zwitterionic at physiological pH
P218	0.13 ± 0.013	0.41 ± 0.022	0.684 ± 0.017	0.88 ± 0.041
JPC3210	0.0028 ± 0.00020c	0.21 ± 0.012	0.227 ± 0.012	0.029 ± 0.0030
Neutral at physiological pH
Dapsone	0.27 ± 0.019	0.63 ± 0.11	Not assessed	0.86 ± 0.059
Dihydroartemisinin	0.21 ± 0.010d	0.34 ± 0.018d	Not assessed	0.87 ± 0.10d
DSM421	0.039 ± 0.007	0.43 ± 0.020	0.615 ± 0.043	0.77 ± 0.065f
Pyrimethamine	0.095 ± 0.0010b	0.46 ± 0.090	0.48 ± 0.034	0.54 ± 0.097
MMV048	0.11 ± 0.0070b	0.46 ± 0.022	0.653 ± 0.060	0.61 ± 0.014
Artemisone	0.12 ± 0.0060	0.46 ± 0.013	Not assessed	0.44 ± 0.024
Artemether	0.038 ± 0.0090c	0.46 ± 0.039	Not assessed	0.50 ± 0.052
SJ733	0.085 ± 0.012c	0.40 ± 0.040	Not assessed	0.58 ± 0.069
DSM265	0.0018 ± 0.00010c	0.18 ± 0.0050f	0.366 ± 0.041	0.28 ± 0.0070f
KAE609	0.0016 ± 0.00010c	0.044 ± 0.0040	Not assessed	0.019 ± 0.0010
OZ439	< 0.0001c	0.010 ± 0.0010	Not assessed	0.0010 ± 0.00010
ELQ300	0.00010 ± 0.000010c	CNDe	0.001 ± 0.001	0.002 ± 0.00010

CND could not determine

^aMean ± SD, n = 3–4 replicates; ultracentrifugation used unless indicated otherwise

^bRED device with diluted plasma correcting for the dilution factor with 6 h dialysis

^cRED device with diluted plasma correcting for the dilution factor; presaturation of device and 24 h dialysis

^dInstability evident; where values are given they represent an estimate only

^eCompound not detected in free fraction

^fData for DSM265 from [79] and for DSM421 from [78]