The Law of Diminishing Returns when increasing drug dosages. This example is based on piperaquine using PK/PD parameters from Table 1 of Winter & Hastings. (A) The drug concentrations post-treatment: the green line is the standard dose of three daily doses of 18 mg/kg given as a single dose of 54 mg/kg (for illustrative purposes), the blue line is a double dose (108 mg/kg), and the red line is a triple dose (162 mg/kg). (B) The Michaelis-Menton relationship between drug concentration and anti-malarial activity. (C) The activity profiles post-treatment of the three different doses, obtained by multiplying the drug concentrations by their killing rate. Doubling the dose gave only an extra 49% area under the drug killing curve while tripling the dose gave only an increase of 19% compared to the double dose. [Figure 5 was constructed using simple PK/PD models and their corresponding equations[26, 29]. Parameter values for the three drugs are as follows: Dose is 54 mg/kg for ‘green’, 108 mg/kg for ‘blue’ and 162 mg/kg for ‘red’; volume of distribution is150 L/kg; elimination rate per day is 0.03 (equivalent to half-life of 23.1 days); maximal drug-killing rate per day (Vmax) is 3.45; IC50 is 0.088 mg/L; slope of dose-response curve (n) is 6].