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The blood circulates ‘around the body’ (termed distribution) to various tissues and provides oxygen and nutrients, and also removes metabolic waste from the tissues; the drug is also distributed to the body tissues through the blood circulation. Therefore, measuring drug concentration in blood gives a reflection of the drug concentration in various body tissues. A blood sample can be more easily obtained from a human volunteer or the patients as compared to the other body tissues. Blood is a complex matrix containing various cellular components (blood cells) and dissolved constituents in the liquid part of the blood. Refer to the schematic in Figure 2.5 to understand how plasma and serum differ from the whole blood.

Typically, when a drug concentration is measured in a whole blood sample, the concentration may not be the same as if measured in serum, or plasma. This is due to the changes in the volume that occur when plasma or serum is separated from the blood as well as potential binding of the drug to blood components, refer the illustration in Box 2.1 for an example to understand this phenomenon.

Often, drugs have a tendency to bind to plasma proteins (like albumin) or the red blood cells (RBCs); in this case, it is necessary to differentiate between the ‘fraction bound’ and the free fraction of drug that is present. The drug concentration measured in plasma or serum may, therefore, specifically refer to the ‘fraction unbound’ of the drug and will not be the same as the total drug concentration in the whole blood. The ‘fraction unbound’ is also termed the ‘free fraction’ of the drug. It is this free fraction that is distributed to the body tissues, exerts its pharmacological effects and is also excreted via urine. The ‘fraction bound’ is usually confined to the blood circulation, is not distributed to the tissues and is often ‘unavailable’ for elimination via the kidneys. The ‘fraction bound’ and ‘fraction unbound’ are maintained in equilibrium, and the fraction bound becomes unbound with time due to a continuous reduction of the unbound fraction following drug elimination.

Figure 2.5 Illustration explaining how plasma and serum differ from blood.