A drug is of no use unless it can be delivered to the patient in an appropriate form at an appropriate site. The way in which a drug is administered to an animal patient is influenced by several factors:

The manufacturing process can have a significant effect on the physical and chemical characteristics of drug molecules that influence their bioavailability. Because of manufacturing differences, the generic equivalent form of a drug may differ somewhat from a trademark form in overall efficacy. Bioavailability often is demonstrated with the use of a blood level curve (Figure 1-3). Factors that may affect the absorption process include the following:

Drug transporters also play a major role in drug absorption. The best described transporter is the P-glycoprotein (P-gp). P-gp is produced at the direction of the MDR1 (ABCB1) gene. It uses adenosine triphosphate (ATP) as an energy source to pump drugs from cells. It is found in most mammalian tissue and appears to act in a protective manner. It is useful in intestinal, renal, placental, liver, and brain tissue, where it helps to pump transported drugs out of the body or away from protected sites. The protection is achieved by pumping the drugs into the intestine, bile, or urine for elimination or away from the fetus or brain (Boothe, 2012).

Some small drug molecules such as electrolytes may simply move with fluid through pores in cell membranes. Active transport of drugs across cell membranes moves molecules from an area of lower concentration to an area of higher concentration and requires that the cell use energy. This is the usual mechanism for the absorption of sodium, potassium, and other electrolytes. In pinocytosis, a third method of passive transport, cells engulf drug molecules by invaginating their cell membrane to form a vesicle that then breaks off from the membrane in the interior of the cell. The method of absorption that occurs in a particular situation depends on whether the drug is fat soluble or water soluble, the size and shape of the drug molecule, and the degree of ionization of the drug.

Many drugs can pass through a cell membrane only if they are nonionized (i.e., not positively or negatively charged). Most drugs exist in the body in a state that consists of both ionized and nonionized forms. The pH of a drug and the pH of the area in which the drug is located can determine the degree to which a drug becomes ionized and thus is absorbed. Weakly acidic drugs in an acidic environment do not ionize readily and therefore are absorbed well. The absorption of basic drugs is more favorable in an alkaline environment. If a drug is placed in an environment in which it readily ionizes, such as a mildly acidic drug in an alkaline environment or a mildly alkaline drug in an acidic environment, it does not diffuse and may become trapped in that environment.

As the absorptive surface of the area of drug placement increases, so does the rate of absorption. One of the largest absorptive surfaces in the body is found in the small intestine because the efficient design of the villi maximizes the surface area.

At any site of drug administration, as the blood supply to an area increases, so does the rate of absorption of the drug. Drugs are absorbed from an intramuscular site at a faster rate than from a subcutaneous site because of the proportionately greater blood supply to the muscle. Initiating the fight-or-flight response increases blood flow to the muscle but decreases blood flow to the intestines. Heat and massage also increase blood flow to an area. Poor circulation, which may occur during shock or cardiac failure, decreases blood flow, as does cooling or elevation of a body part. These factors then can positively or negatively influence drug absorption.

Another important factor that determines the rate at which drugs pass across cell membranes is the solubility of the drug. The lipid (fat) solubility of a drug tends to be directly proportional to the degree of drug nonionization. As was stated previously, the nonionized form is the one that usually is absorbed. The degree of lipid solubility of a drug often is expressed as its lipid partition coefficient. A high lipid partition coefficient indicates enhanced drug absorption.

Drug absorption rates often depend on the formulation of the drug. Various inert ingredients, such as carriers (vehicles), binding agents, and coatings, are used to prepare dosage forms. These substances have major effects on the rate at which formulations dissolve. Depot and spansule are terms that are associated with prolonged- or sustained-release formulations in veterinary medicine. Subcutaneous implants that contain growth stimulants that break down slowly and release their products over prolonged periods are used in some situations.

When drugs are given orally, the condition of the GI tract can have a major influence on the rate and extent of drug absorption. Factors such as degree of intestinal motility, emptying time of the stomach, irritation or inflammation of the mucosa (e.g., gastritis, enteritis), damage to or loss of villi (e.g., viral diseases), composition and amount of food material, and changes in intestinal microorganisms can affect the rate and extent of absorbance of medications. Another consideration regarding drugs that are absorbed from the GI tract is the first-pass effect. This refers to the fact that substances are absorbed from the GI tract into the portal venous system, which delivers the drug to the liver before it enters the general circulation. In some instances, a drug then is metabolized in the liver to altered forms; this process may make the drug inactive or less active.

The process of combining some drugs with other drugs or with certain foods can negatively affect drug absorption. The availability of tetracycline is reduced if it is administered with milk or milk products. Antacids may reduce the absorption of phenylbutazone or iron products. Technicians always should consult appropriate references about potential interactions before administering new drugs.

Drug distribution is the process by which a drug is carried from its site of absorption to its site of action. Drugs move from the absorption site into the plasma of the bloodstream, from the plasma into the interstitial fluid that surrounds cells, and from the interstitial fluid into the cells, where they combine with cellular receptors to create an action. Equilibrium soon is established between these three compartments while the drug moves from the blood into the tissue and then from the tissue back into the blood (Figure 1-4). How well a drug is distributed throughout the body depends on several factors.