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A safe method for rapidly achieving plasma concentration plateaus
Author(s) -
Wagner John G.
Publication year - 1974
Publication title -
clinical pharmacology and therapeutics
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.941
H-Index - 188
eISSN - 1532-6535
pISSN - 0009-9236
DOI - 10.1002/cpt1974164691
Subject(s) - steady state (chemistry) , plasma concentration , elimination rate constant , plasma , chemistry , pharmacokinetics , intravenous bolus , reaction rate constant , constant (computer programming) , bolus (digestion) , mathematics , analytical chemistry (journal) , chromatography , kinetics , pharmacology , anesthesia , physics , medicine , computer science , volume of distribution , quantum mechanics , programming language
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.