The kinetics of insecticide action. Part IV:the in‐vivo distribution of pyrethroid insecticides during insect poisoning

摘要

AbstractThe distribution of pyrethroids in insects has been studied using a combination of mathematical modelling and experimental observation. This approach has resulted in the formulation of a physiological model of the pharmaco‐kinetics of cypermethrin applied topically to larvae of Spodoptera littoralis. Development of this model from simpler two‐ and three‐compartment models is described. Simple models, whilst capable of complex behaviour, consider only the average rates and magnitudes of pharmaco‐kinetic processes over whole animals, and cannot account for differences in concentration of insecticide between individual tissues. This can be achieved by using physiological models, but these require more experimental information for their validation. Moreover, unless simplifying assumptions are made, analytical solutions are not feasible for the large number of equations necessary to define such models.The modelling studies prompted an investigation of (1) in‐vivo binding of insecticide to insect tissues, (2) the sizes of body compartments, and (3) the factors which affect the distribution of toxicant between these compartments. Binding has a marked effect on pharmacokinetic profiles and may result in oscillatory behaviour. During poisoning, the total bound cypermethrin increases proportionally to the cube root of the elapsed time. This results in a rapid rate of increase over early elapsed times (<3h) which slows to approach a more linear form thereafter. Average sizes for the body compartments of larvae of Spodoptera littoralis Boisd, and the steady‐state distribution of cypermethrin in these compartments are described. Although the haemolymph, which acts as the main distributive phase during poisoning, forms the largest compartment by volume, it has a low affinity for cypermethrin and distribution reaches steady state within 5 min after topical application. The nerve cord (the target tissue), which is the smallest compartment, has the highest steady‐state concentration of cypermethrin. The distribution of cypermethrin in larval tissues is related to the ratios of tissue dry matter to