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■Bio-mathematics, Statistics and Nano-Technologies: Mosquito Control Strategies

Figure 10.2: Illustrating a pharmacokinetic two-compartment model and associated rate

constants.

• develop the economic case for sustainable investment that takes account of the needs

of all countries, and increase investment in new medicines, diagnostic tools, vaccines

and other interventions.

So far, ACTs that have been tested remain highly efficacious. However, further spread of

resistance to artemisinin and ACT partner drugs could pose a major public health challenge

and jeopardize important gains in malaria control. Regular monitoring of drug efficacy

is needed to inform treatment policies in malaria-endemic countries, and to ensure early

detection of, and response to, drug resistance.

10.4

CLINICAL PHARMACOKINETICS OF ANTIMALARIAL DRUGS

The two-compartment pharmacokinetic model fit for artemether and lumefantrine,

demonstrated by a few studies for both drugs administered through the extravascular

(mostly oral) route [21, 22, 23, 24]. The two-compartment model has is made up of a cen-

tral compartment representing plasma and highly perfused tissues and a peripheral com-

partment which represents all the tissues and organs of the human body. There is bidirec-

tional movement of the antimalarial drug between the central and peripheral compartments

with drug input and elimination occurring from the central compartment (Figure 10.3).

The two-compartment model pharmacokinetics describes three main phases of absorption,

distribution, and elimination with rate constants α,β(K10), respectively with assumptions

that absorption, distribution, metabolism and elimination processes follow first order ki-

netics and the movement of drugs between compartments is through passive diffusion. In

addition, it assumes that the antimalarial concentration measurements are from blood and

the organ of elimination is in the central compartment.

The parameters of a two-compartment model extravascular administration include: the

absorption rate constant (Ka), the rate constant from central to the peripheral compartment

(K12), and reverse (K21), the distribution coefficient (A) and rate constant (α), the volume

of distribution (V c,V ss,V z), the elimination coefficient (β) and rate constant (K10), the

elimination half-life (t½), the area under the concentration-time curve (AUC) and clearance

(Cl).

The distribution of the free fraction between central and peripheral compartment is

dependent on the rate constants of movement of drug molecules in and out of the two

compartments. The elimination rate constant (K10) describes the rate of removal or elimi-