Pharmacological Approach to Combat Mosquito Transmitted Malaria
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Table 10.3: Estimating that a 6 month old child is about 5kg, the dosing will be as follows
as well as the maximal plasma concentration.
Artemether
Lumefantrine
Method
Dchild
Cmax
Dchild
Cmax
(80 mg adult)
µg/mL
(480 mg adult)
µg/mL
WHO guidelines
20 mg
4.44
120 mg
7.50
Yong’s
3.2 mg
0.71
19.2 mg
1.20
Salomon (Fried)
3.2 mg
0,71
19.2 mg
1.20
Webster
16 mg
3.56
96 mg
6.00
Clark
6 mg
1.33
35 mg
2.19
Metabolic ratio
17 mg
3.56
99 mg
6.19
Adult dose
80 mg
0.37 *
480 mg
4.66
* Based on adult values of Vd, being 3.1 L/kg for artemether [20] and 1.47 L/kg for
lumefantrine [39].
where Wchild is the weight of the child in kilograms.
Using the pharmacokinetic values available, however, the dose (D) may be based on
the target plasma concentration (Cp) and calculated using following equation:
Cp =
FDka
Vd (ka −ke)
e−ket −e−kat
(10.20)
where F is the bioavailability and ka is the absorption rate constant. Here, the target con-
centration could be 186 ng/mL for artemether [38] and 8 µg/mL for lumefantrine [38],
which is the measured plasma concentration 2 and 6 hours after the administration of an
adult dose to adults, respectively. Using the equations, the new dose may be calculated as
shown in Table 10.3. Here, an important factor that must be taken into the account, is that
the pharmacokinetics in children, such as volume of distribution (Vd) and the half-life, is
quite different, compared to adults.
For artemether the Vd has been found to be around 8 L/kg and the half-life is about
1.6 hours for adults [38, 40], compared to Vd for the central compartment of 2.8 L/kg and
15.3 L/kg for the peripheral compartment, in children [41]. The half-life in children was
found to be 3.9 hours [42]. The bioavailability for artemether tablets is found to be 43.2%
[40]. For lumefantrine the Vd has been found to be around 1.5 L/kg and the half-life is
about 95 hours [38] for adults, compared to Vd for the central compartment of 0.75 L/kg
and 3.2 L/kg for the peripheral compartment, in children. Tchaparian et al. [43], however,
found significant higher Vd for lumefantrine, or 53,2 L/kg. The half-life in children was
found to be 17.9 hours [44]. The bioavailability for lumefantrine tablets is found to be 57%
for crushed tablets, and 65% with dispersible tablets [23]. Based on the short half-life in
children, compared to adults, they may need more frequent and longer dosing scheme, than
with adults.