Rapidly achieved plasma concentration plateaus, with observations on theophylline kinetics

Many therapeutic agents can be applied more predictably and effectively if a constant plasma concentration is maintained. With the use of the two‐compartment open‐system model, a general and practical method of combining intravenous bolus and continuous infusion is described. The fastest approach to the plateau situation is shown to result from setting the maintenance infusion rate equal to β times the initial bolus, where β is the slower disposition constant. This procedure was verified in 3 normal subiects. Single bolus doses of theophylline were administered to study the pharmacokinetic behavior of this drug in each individual. This information was used to calculate the regimen required to reach a predetermined plateau concentration. The selected bolus and continuous infusion were given, and in each case resulted in constant plasma values within the first hour.