Figure1: Example of variability in plasma drug concentration amongsubjectsgiven the same drug dose Figure 1 source: https://www.ashp.org/-/media/store%20files/p2418-sample-chapter-1.pdf2Basicconcepts of TDM2.1Therelationship between a drug dose, drug serum concentration, and drug effectThe discipline of pharmacokinetics (PK) appliesmathematical models to portray and study themetabolic processes and relationships between drug dose and drug concentrationin serum and other biologic fluids (Greenblatt and Shader 1985).
Pharmacodynamics (PD) appliessimilar models to comprehend the time course of drug activities on the body(Figure 2A). Physicians are most worried about pharmacodynamics—they need to knowhow drug dose, route, and frequency of administration can be used to maximizethe effect and minimize the side effects. This relationship between a drug dose and a drug serumconcentration is determined mainly by a major factor which is drug availability, a process that varies substantially among patients,and within a patient (Aronsonet al.
1992). Because of thesereasons, it is vital to understand that the actual drug dose may have littlepredictive value, and knowledge of drug concentration can make the differencebetween a failed versus an optimal treatment response. The availability of adrug especially with oral agents depends on the degree of absorption and forsome drugs, the extent of the so-called first-pass metabolism (Gibaldi et al.1971). The decrease in thefraction of drug absorbed is equivalent to a decrease in the dose given. Forinstance, if we have 100 % of oral agents ingested, that amount will go throughthe stomach then to the small intestine, at the level of enterocytes there aremultiple enzymes such as Cytochrome P450 that metabolize drugs and decrease theamount available. Also drug transporters like P glycoproteins at the wall ofintestine which pump the drug out, further decreasing the amount that can beabsorbed down to 50%. The remaining percent travel through the portal vein tothe liver where at the level of hepatocytes will have a similar mechanism thatwould decrease the amount of drug available for systemic effect (Figure 2B).