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Pharmacokinetic control and clinical interpretation of steady‐state blood levels of drugs
Author(s) -
Levy Gerhard
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/cpt1974161part2130
Subject(s) - pharmacokinetics , steady state (chemistry) , drug , pharmacology , dosing , distribution (mathematics) , chemistry , absorption (acoustics) , half life , medicine , mathematics , materials science , mathematical analysis , composite material
Avemge steady‐state blood leveL~ are a function ot the dose, fraction of dose absorbed, dosing interval, biologic half‐life, and apparent voZume of distribution of drugs that have apparently linear pharmacokinetic characteristics. The rate of accumuLation of such drugs, when admini5tered at regular intervals, is inversely proportional to the half‐life of their slowest (terminal) elimination phase. “Hidden accumulation” may occur if the terminal elimination phase of a drug reflects the characteristics of a reLatively very small pharmacokinetic compartment; this may account for a gradual increase in the intensity of a pharmacologic efJect at a time when drug concentrations in plasma are apparently at the steady state. Fluctuations of drug levels du ring a dosing interval at the steady state due to the effects of absorption, distribution, and elimination can complicate the assessment and interpretation of these levels. Contra I of steady‐state levels is particularly difficult in the case of drugs with distinct nonlinear (Michaelis‐Menten) characteristics; a change in dose (or fraction absorbed) will cause a more than proportional change in the steady‐state drug level. The clinical interpretation of steady‐state drug levels must take into consideration the possible effects of pharmacologically active metabolites and of changes in drug distribution that may modify the relationship between drug concentration in plasma and the intensity of a pharmacologic efJect.