Pharmacological Approach to Combat Mosquito Transmitted Malaria

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During the second and third trimesters, uncomplicated P. falciparum malaria must be

treated using ACTs, although safety assessment of artemether and lumefantrine is still

ongoing, pharmacokinetics and effectivness as well as its effectiveness [10]. Safety studies

in more than 4000 pregnancies, report no adverse effects on both mother and fetus. Certain

antimalarial drugs, however, such as primaquine should not be used during pregnancy. The

fetus is constantly growing. First slowly, but during second and third trimester it starts

growing rapidly, making the fetoplacental compartment (10.4) under constant change. The

volume of this compartment (Vpreg) can be described by the Gompertz equation:

Vpreg = ae^{( b}

c^{)(1−e−cGA)}

(10.10)

where GA indicates the gestational age in weeks and a, b and c are constants, that are equal

to 0.01, 0.37 and 0.52, respectively [31]. After the intake of a drug, the changes in the drug

concentration in the fetoplacental compartment can be described by [32] as follows:

d

VpregCpreg

dt

= Qpreg



Cab −^Cpreg

Kpreg:P

B:P





(10.11)

Here, the Cpreg is the drug concentration in the fetoplacental compartment, Qpreg is

the blood flow to the compartment, Cab is the concentration in the incoming arterial

blood, Kpreg:P is the fetoplacental compartment:plasma partition coefficient and B:P is the

blood:plasma concentration ratio (0.7 for artemether and 0.6 for lumefantrine,[33]). To

complicate things even more, all these parameters are dependent on the gestational time.

Malaria affects the placenta quite hard, resulting in spontaneous miscarriage, stillbirth,

or neonatal mortality [15]. If the fetus survives the placental sickness, it will probably

have lower birth weight. Due to this, all pregnant women are recommended to use anti-

malarial drugs such as sulfadoxine-pyrimethamine during pregnancy, reducing the placen-

tal parasitaemia by about 50%. Pregnant women in their first trimester should avoid using

artemether/artesunate and lumefantrine, but to use quinine and clindamycin instead [15].

10.6

TREATMENT OF INFANTS AND YOUNG CHILDREN

After birth, the organs are continuing their maturation and necessary functions such

as the liver and the kidneys. Elimination, for example, of drugs from newborns can be

very slow. So, infants and children may metabolize and excrete drugs, such as antimalarial

drugs, quite differently from adults. It takes time for the liver enzymes to mature. The

maturation of the liver enzymes, expressed as the ratio of enzymes compared with humans

can be described as follows [35], for each enzyme:

CY P2C9

=

0.17+

0.81.Age^0.53

0.0157^0.53 +Age^0.573

(10.12)

CY P2C19

=

0.3+

0.68Age^2.44

0.29^2.44 +Age^2.44

(10.13)