تسجيل الدخول

تسجيل

Distribution of drugs into tissues

المؤلف:  Sue Jickells , Adam Negrusz (Editors)

المصدر:  Clarkes Analytical Forensic Toxicology

الجزء والصفحة:  17

2026-09-13

20

Distribution of drugs into tissues

The uptake of drugs (distribution) into tissues depends on a number of factors. These include the blood flow to the tissues, the partition coefficient of the drug between blood and the tissue, the degree of ionization of the drug at the pH of plasma, the molecular size of the drug and the extent of tissue and plasma protein binding. For example, the distribution of plasma protein bound drugs such as the warfarin-type anticoagulants is restricted to plasma and extracellular fluid, whereas alcohol distributes equally into the total body water. The approximate volumes of the body water compartments for a person of average weight are 25 L for intracellular water and 17 L for extracellular water (of which 3 L is plasma water). An intravenous dose of a drug distributed immediately and equally into the total body water (approximately 42 L) gives an initial plasma concentration (dose divided by 42) approximately two-fifths of that obtained if the same dose were distributed only into extracellular water (dose divided by 17). If the drug is extensively bound to tissue proteins, an even lower initial plasma concentration is obtained, and the volume term relating the dose to the plasma concentration can exceed the volume of the body. The approximate proportions of drugs with particular volumes of distribution in the plasma water are given in Table 2.2.

The instantaneous equilibrium of drug concentrations throughout the body does not necessarily require that the concentrations be equal throughout the body. In fact, drug concentrations in tissues are rarely equal to those in plasma. For example, the tissue: plasma concentration ratio is very low immediately after intra venous administration because it takes time for the drug to transfer from the blood to tissues. As time progresses, the amount of drug in the tissue compartment increases and, like that in the plasma compartment, eventually reaches a maximum. If the drug is stored actively in a particular tissue compartment, the ultimate concentration ratio between the tissue and plasma will be relatively high. Note also that the tissue: plasma concentration ratio depends not only on the processes of distribution but also to a large extent on the route of drug administration and on whether single or multiple doses are given. Knowledge of how a particular drug or metabolite partitions between blood and tissues is important in interpreting analytical results, particularly where only one sample type (e.g. blood but not tissue) has been analysed.