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Table 2 An ideal Target Product Profile (TPP) for an anti-malarial combination therapy

From: Pharmacological considerations in the design of anti-malarial drug combination therapies – is matching half-lives enough?

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]
  1. KPC: key pharmacological consideration.