Table 8.

In vitro metabolism in human liver microsomes

Compound	HLM CL_int (µL/min/mg)^a	Unbound CL_int (µL/min/mg)
Ionized or partially ionized bases at physiological pH
Cycloguanil	< 7^b	< 9.72^c
Doxycyclin	< 7^b	< 7.53^c
Pyronaridine	8.6	29.7
Proguanil	< 7^b	< 21.2^c
Primaquine	7.70	13.8
Chloroquine	< 7^b	< 14^c
Chlorproguanil	< 7^b	< 135^c
Azithromycin	< 7^b	< 10^c
AQ-13	< 7^b	< 10.6^c
Desethylamodiaquine	13.3	CND^d
Quinine	16.5	28.9
Clindamycin	32.0	47.8
KAF156	14.7	105
M5717	11.1	22.2
OZ277	< 7^b	< 159
Mefloquine	< 7^b	< 140^c
Amodiaquine	308	339
NPC1161B	< 7^b	CND
Ferroquine	29.2	108
Naphthoquine	14.4	68.6
Tafenoquine	< 7^b	< 3500^c
MMV253	13.2	120
MMV052	13.0	13,000
Piperaquine	20.1	1540
Halofantrine	26.9	13,500
TDD-E209	25.5^e	85,000
Lumefantrine	< 7^b	CND^d
Ionized acids at physiological pH
Sulfadoxine	< 7^b	< 7.53
Sulfamethoxazole	< 7^b	< 7.00
Artesunate	146	CND^d
Atovaquone	< 7^b	< 3500^c
Zwitterionic or partially zwitterionic at physiological pH
P218	< 7^b	< 7.95^c
JPC3210	9.50	328
Neutral at physiological pH
Dapsone	< 7^b	< 8.14^c
Dihydroartemisinin	16.6	19.1
DSM421	< 7^b	< 9.09^c
Pyrimethamine	< 7^b	< 13^c
MMV048	< 7^b	< 11.5^c
Artemisone	97.7	222
Artemether	163	326
SJ733	142	245
DSM265	< 7^b,e	< 25^c
KAE609	24.1	1270
OZ439	72.1	72,100
ELQ300	< 7^b	< 3500^c

^aAverage of n = 2 replicates

^b< 15% loss over 60 min

^c“less than” CL_int values corrected for measured microsomal binding

^dCND = could not determine, plasma or microsomal f_u value not available

^eData for DSM265 from [79] and for TDD-E209 from [81]