Figure determined mainly by a major factor which is

Figure
1: Example of variability in plasma drug concentration among

subjects
given the same drug dose

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Figure 1 source: https://www.ashp.org/-/media/store%20files/p2418-sample-chapter-1.pdf

2

Basic
concepts of TDM

2.1The
relationship between a drug dose, drug serum concentration, and drug effect

The discipline of pharmacokinetics (PK) applies
mathematical models to portray and study the
metabolic processes and relationships between drug dose and drug concentration
in serum and other biologic fluids (Greenblatt and Shader 1985). Pharmacodynamics (PD) applies
similar models to comprehend the time course of drug activities on the body
(Figure 2A). Physicians are most worried about pharmacodynamics—they need to know
how drug dose, route, and frequency of administration can be used to maximize
the effect and minimize the side effects.

This relationship between a drug dose and a drug serum
concentration is determined mainly by a major factor which is drug availability, a process that varies substantially among patients,
and within a patient (Aronson
et al. 1992). Because of these
reasons, it is vital to understand that the actual drug dose may have little
predictive value, and knowledge of drug concentration can make the difference
between a failed versus an optimal treatment response. The availability of a
drug especially with oral agents depends on the degree of absorption and for
some drugs, the extent of the so-called first-pass metabolism (Gibaldi et al.
1971). The decrease in the
fraction of drug absorbed is equivalent to a decrease in the dose given. For
instance, if we have 100 % of oral agents ingested, that amount will go through
the stomach then to the small intestine, at the level of enterocytes there are
multiple enzymes such as Cytochrome P450 that metabolize drugs and decrease the
amount available. Also drug transporters like P glycoproteins at the wall of
intestine which pump the drug out, further decreasing the amount that can be
absorbed down to 50%. The remaining percent travel through the portal vein to
the liver where at the level of hepatocytes will have a similar mechanism that
would decrease the amount of drug available for systemic effect (Figure 2B).

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