A safe method for rapidly achieving plasma concentration plateaus

The classical procedure of administering a loading dose as a bolus intravenous iniection and at the same time starting an infusion at a constant rate could be dangerous or lead to toxicity with certain drugs. Under such conditions the ratio of the initial plasma concentration (C o 1 ) to the steady‐state plasma concentration (C eq 1 ) is often large. The higher the ratio of drug in tissues/drug in plasma (i.e., the more "two compartment" the drug is) the higher will be the C o 1 /C eq 1 ratio. A method is proposed in which initially a constant‐rate infuSion at the rate of Q 1 is given over T hours (0.25 to 3 hr); then the rate is abruptly changed to a lower rate Q 2 which is maintained as long as steady state is desired. A simple relationship is given that shows what the ratio of Q 1 Q 2 must be to attain steady state most rapidly and to minimize the ratio C MAX 1C /C eq where C MAX 1 is the maximum plasma concentration attained at time T, iust as the infusion at the higher rate ceases. A simple linear graph is given that allows rapid determination of the needed ratio Q 1 Q 2 Variables needed for a given drug to use the method are plasma clearance and plasma half‐life.