Table 2.

An ideal Target Product Profile (TPP) for an anti-malarial combination therapy

Property		Attribute	Reference
Formulation & dose	Single-dose treatment regimen	Desirable	[17,32]
	Stable	Critical	[32]
	Fixed-dose in a single formulation	Desirable	[32]
	Orally, rectally and parentally applicable	Desirable	[32]
	Dose of each drug high enough so that it will remain effective even if resistance is present to the other drug	Critical	This manuscript KPC#4
Mode of action	Effective against all stages of parasite development in the human host	Desirable	[32]
	Active against hypnozoites and able to prevent relapse	Desirable	[17]
	Transmission-blocking activity	Desirable	[17]
	Robust to the evolution of resistance	Critical	[32]
	Independent, or preferably synergistic, mode of action of drugs	Desirable	[32]; this manuscript KPC#4
	Different metabolic target(s) of drug action	Desirable/Critical	This manuscript KPC#4
	Negative patterns of cross resistance	Desirable	This manuscript KPC#6
Pharmacokinetics & pharmacodynamics (PK/PD)	Elimination half-lives of drugs should be approximately matched	Desirable	[32,33]
	The post-treatment drug activity profiles (based on elimination half-lives, dosages and drug sensitivity) should be matched	Critical	This manuscript KPC#1 (Figures  2 & 3)
	Low levels of inter-individual PK/PD variation to minimise drug activity profile mismatch in individual infections	Desirable	This manuscript KPC#2 (Figure  4)
	Extended period of chemoprophylaxis post-treatment	Desirable	[15,17]
	Predictable metabolism via non polymorphic enzymes	Desirable	This manuscript KPC#5
	No pharmacokinetic drug-drug interaction	Desirable	This manuscript KPC#5
Efficacy & safety	Large therapeutic index	Desirable	This manuscript KPC#3
	Toxicity of drugs should be additive or antagonistic	Desirable	This manuscript KPC#3
	Drug conversion and elimination should not share same metabolic pathway	Desirable	This manuscript KPC#3
	Dissimilar type B adverse drug reaction profiles	Desirable	This manuscript KPC#3
	Safe and well-tolerated	Critical	[32]
	Efficacious and effective	Critical	[32]
Cost	Affordable/cheap	Critical	[17,32]

KPC: key pharmacological consideration.