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

• For extravascular administration, the bioavailability is added as described above. The

volume of distribution at steady state (Vss) is described below:

Vss = Vc

(K12 +K21)

K21

,

(10.6)

or where the denominator K21 is replaced with α.

The Vc and the Vss are the most useful volumes, they can be used in calculation of initial

concentration and the loading dose, respectively.

The absorption phase has three processes: absorption, distribution and elimination oc-

curring simultaneously with absorption being dominant leading to the overall transfer of

drug from absorption site into the central compartment. The absorption rate constant for

a two-compartment model is determined by feathering or by using the Loo-Reigelman

method that requires intravenous administration of the drug in addition to the extravascular

route, the equation for fraction of drug absorbed at a time point (Ft) is as follows:

Ft =

(Cp)t +

K10AUC0−∞(Xperi)t

Vc

K10AUC0−∞

(10.7)

Xperi represent the amount of drug in the peripheral compartment.

The absorption of lumefantrine is first order with a lag time and a time to maximum

concentration (tmax) of 6 hours. The fraction of dose absorbed increases with increased fat

content in food with factor of 16. In the fasted state, absorption decreases by approximately

10 percent. These differences due to diet content can be one of the contributory factors to

the individual variability in bioavailability [23, 25] with significant improvements in model

data description with the incorporation of inter-individual variability in Ka.

In malaria, the disease itself, affects food intake and thus causing variations in the ab-

sorption of lumefantrine with parasite count, leading to decrease in bioavailability seen

with high counts, and high bioavailability achieved with clinical recovery from Malaria.

The increase in bioavailability with treatment progression is attributable to a return to

normal food intake that comes with clinical improvement after the first dose. Various

drugs may affect the bioavailability of malarial drugs, such as efavirenz that reduces the

bioavailability of lumefantrine. Artemether is absorbed more rapidly with a tmax of approx-

imately 2 hours. The bioavailability of artemether increases two-fold with an increase in

dietary fat content. There is marked variability in the absorption of artemether in malaria

patients. There is no evidence of clinically significant effects on the bioavailability of

artemether caused by concomitantly administered drugs. However, grapefruit juice may

increase plasma levels of artemether in plasma and the extent of interaction is dependent

on volume of juice consumed.

Following oral administration lumefantrine and artemether are extensively distributed

into body tissues and highly protein bound with over 90% of the two being bound to plasma