As artemisinin combination therapies (ACTs) are compromised by resistance, we are evaluating triple combination therapies (TACTs) comprising an amino-artemisinin, a redox drug and third drug with different mode of action. Thus, here we briefly review efficacy data on artemisone, artemiside, other amino-artemisinins and 11-aza-artemisinin, and conduct ADME profiling
in vitro
and PK profiling
in vivo
via iv and po administration to mice. The sulfamide derivative has a notably long murine microsomal half-life (
t
1/2
>150 min), low intrinsic liver clearance and total plasma clearance rates (
CL
int
189.4,
CL
tot
32.2 mL/min/kg), and high relative bioavailability (F 59%). Kinetics are somewhat similar for 11-aza-artemisinin (
t
1/2
>150 min,
CL
int
576.9,
CL
tot
75.0 mL/min/kg), although bioavailability is lower (F 14%). In contrast, artemether is rapidly metabolized to DHA (
t
1/2
17.4 min) and eliminated (
CL
int
855.0,
CL
tot
119.7 mL/min/kg), and has low oral bioavailability F of 2%. Whilst artemisone displays low
t
1/2
of <10 min and high
CL
int
of 302.1, it displays a low
CL
tot
of 42.3 mL/min/kg, and moderate bioavailability F of 32%. Its active metabolite M1 displays a much improved
t
1/2
of >150 min and a reduced
CL
int
of 37.4 mL/min/kg. Artemiside has
t
1/2
12.4 min and
CL
int
673.9 and
CL
tot
129.7 mL/kg/min, likely a reflection of its surprisingly rapid metabolism to artemisone, reported here for the first time. DHA is not formed from any amino-artemisinin. Overall, the efficacy and PK data strongly support the development of selected amino-artemisinins as components of new TACTs.