Revisiting the effect compartment through timing errors in drug administration

The variations in the pharmacological effects induced by timing errors in drug intake are compared for two drugs, one acting by way of an effect compartment and the other directly from the central compartment. A simulation was performed for two drugs having the same concentration-effect relationship at the receptor site, the same mean effect at equilibrium and identical concentrations in the central compartment. In this article, Patrice Nony, Michel Cucherat and Jean-Pierre Boissel discuss how, for the same variability of concentrations in the central compartment, the variations in mean effects are different. When there is large variability in the interval separating two consecutive doses, the model that includes an effect compartment dampens the pharmacokinetic variability present in the central compartment. Such an approach may be useful for the prescription recommendations of drugs, especially those with narrow therapeutic indices.