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Figure 3 | Malaria Journal

Figure 3

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

Figure 3

How altering relative dosages can compensate for differences in half-live and/or endogenous anti-malarial activity. (A) The half-lives of two drugs in this CT differ by a factor of 2, leading to one drug being left as a vulnerable monotherapy; most arguments on design of CT end here by concluding the drugs are not well matched. (B) The drug kill rates against parasites as a function of drug concentration; they differ in their IC50 values. (C) Compensating for differing half-lives and IC50s by increasing the dosage of drug illustrated in ‘red’ 2.5 fold: killing is now matched and drugs provide mutual protection. [Figure 3 was constructed using simple PK/PD models and their corresponding equations[26, 29]. Parameter values for the two drugs are as follows: Dose is 75 mg/kg for ‘blue’ and 187.5 mg/kg for ‘red’; volume of distribution is 150 L/kg; elimination rate per day is 0.05 for ‘blue’ and 0.1 for ‘red’ (equivalent to half-lives of 13.8 and 6.9 days, respectively); maximal drug-killing rate per day (Vmax) is 3.45; IC50 is 0.088 mg/L for ‘blue’ and 0.044 mg/L for ‘red’; slope of dose-response curve (n) is 6].

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