drugs
Drug Distribution
Introduction
Drug distribution refers to the movement of a drug to and from the blood and various tissues of the body (for example, fat, muscle, and brain tissue) and the relative proportions of drug in the tissues. (See also Introduction to Administration and Kinetics of Drugs .) After a drug is absorbed into the bloodstream (see Drug Absorption ), it rapidly circulates through the body. The average circulation time of blood is 1 minute. As the blood recirculates, the drug moves from the bloodstream into the body’s tissues. Once absorbed, most drugs do not spread evenly throughout the body. Drugs that dissolve in water (water-soluble drugs), such as the antihypertensive drugatenolol, tend to stay within the blood and the fluid that surrounds cells (interstitial space). Drugs that dissolve in fat (fat-soluble drugs), such as the antianxiety drugclorazepate, tend to concentrate in fatty tissues. Other drugs concentrate mainly in only one small part of the body (for example, iodine concentrates mainly in the thyroid gland) because the tissues there have a special attraction for (affinity) and ability to retain that drug. Drugs penetrate different tissues at different speeds, depending on the drug’s ability to cross membranes. For example, the antibioticrifampin, a highly fat-soluble drug, rapidly enters the brain, but the antibiotic penicillin, a water-soluble drug, does not. In general, fat-soluble drugs can cross cell membranes more quickly than water-soluble drugs can. For some drugs, transport mechanisms aid movement into or out of the tissues. Some drugs leave the bloodstream very slowly because they bind tightly to proteins circulating in the blood. Others quickly leave the bloodstream and enter other tissues because they are less tightly bound to blood proteins. Some or virtually all molecules of a drug in the blood may be bound to blood proteins. The protein-bound part is generally inactive. As unbound drug is distributed to tissues and its level in the bloodstream decreases, blood proteins gradually release the drug bound to them. Thus, the bound drug in the bloodstream may act as a reservoir for the drug. Some drugs accumulate in certain tissues (for example,digoxinaccumulates in heart and skeletal muscles), which can also act as reservoirs of extra drug. These tissues slowly release the drug into the bloodstream, keeping blood levels of the drug from decreasing rapidly and thereby prolonging the effect of the drug. Some drugs, such as those that accumulate in fatty tissues, leave the tissues so slowly that they circulate in the bloodstream for days after a person has stopped taking the drug. Distribution of a drug may also vary from person to person. For instance, obese people may store large amounts of fat-soluble drugs, whereas very thin people may store relatively little. Older people, even when thin, may store large amounts of fat-soluble drugs because the proportion of body fat increases with age. 