The effect of infusion time on the time course of drug concentration in blood

We have studied by digital computer stimulation the relationship among the rate of intravenous infusion of the dose of a drug, the pharmacokinetic parameters of the drug, the maximum blood drug concentration achieved (Cmax) and the interval (TEff) during which the blood concentration of the drug is maintained above a selected minimum effective concentration (CEff) for the case of single dose administration of a drug with monoexponential pharmacokinetics. It was found that increasing the time during which the dose of the drug is infused results in a much smaller decrease in the maximum blood concentration attained. TEff, was found to be a fraction of the ratios infusion time/drug elimination half-life and zero-time intercept (Co)/CEff. The stimulations showed that TEff varies nonlinearly with increasing infusion time. However, the nature of the relationship between TEff and infusion time depends very much on the value of Co/CEff. At low values of Co/CEff, TEff decreased almost linearly with increasing infusion time, but at higher values of Co/CEff, TEff increased for a time with increasing infusion time. From these simulations, it should be possible to predict whether therapeutically effective blood concentrations of a drug may be achieved with the use of a slower infusion in situations where clinical considerations necessitate that the infusion time of the dose be increased.