Raymond K, Morgan D J
J Pharmacokinet Biopharm. 1980 Dec;8(6):573-82. doi: 10.1007/BF01060054.
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.
