Property | Attribute | Reference | |
---|---|---|---|
Formulation & dose | Single-dose treatment regimen | Desirable | |
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 | |
The post-treatment drug activity profiles (based on elimination half-lives, dosages and drug sensitivity) should be matched | Critical | ||
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 | ||
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 |