2 Absorption and Distribution
Learn how administration routes and drug properties affect absorption into the blood, bioavailability, and subsequent movement between blood and tissues.
and
describes how a drug moves through the body. is movement from the administration site into systemic circulation, while is the reversible movement of drug between blood and tissues.
Intravenous (IV) drugs enter the circulation directly, so they bypass as a pharmacokinetic step. Once a drug is in the blood, its is shaped by tissue blood flow, barriers, drug properties, binding, and physiology.
Routes of administration
The route of administration affects where a drug enters the body, how quickly it reaches the circulation, and how much reaches it. Routes are not interchangeable: the same drug can have different and depending on its route and formulation.
Oral: The drug is swallowed and absorbed mainly from the gastrointestinal tract. may be incomplete, and drug reaching the gut may be metabolized in the intestinal wall or liver before entering systemic circulation; this is the .
Sublingual or buccal: The drug is absorbed through tissues under the tongue or in the cheek. These routes can avoid much of gastrointestinal and hepatic first pass.
Rectal: occurs through the rectal lining. The extent of first-pass avoidance varies with the site of .
Parenteral: Injection routes include IV, intramuscular (IM), and subcutaneous (SC). IV administration delivers drug directly into the circulation. IM and SC drugs must move from the injection site into the blood, and is influenced by local blood flow and formulation.
Inhaled: Drug is delivered to the respiratory tract; it may be absorbed across lung surfaces or produce a local effect.
Topical or transdermal: Topical drugs are applied to the skin, often for local effects. Transdermal formulations are designed to cross the skin and enter systemic circulation.
, denoted by , is the fraction of an administered dose that reaches systemic circulation as unchanged drug. IV administration has , or , because the drug is delivered directly into the blood. after other routes may be lower because is incomplete, the drug degrades, or first-pass metabolism occurs.
measures the extent of systemic availability. The rate of also matters because it affects how quickly drug concentrations rise.
Absolute for the same drug can be estimated by comparing dose-normalized exposure, often measured as the area under the plasma concentration–time curve (), after a non-IV route with exposure after IV administration. If an oral dose produces half the dose-normalized of an IV dose, its approximate absolute is , or .
What affects
depends on properties of both the drug and the person receiving it. These influences can change how quickly or how completely drug becomes available in systemic circulation.
Drug properties: Solubility, particle size, formulation, and ability to cross membranes affect how readily a drug becomes available for .
Route and dosage form: A solution, immediate-release tablet, and extended-release tablet can differ in how quickly drug becomes available. The route determines which barriers the drug must cross.
Local conditions: Blood flow, surface area, and the condition of the absorbing tissue can alter . For oral drugs, food and gastrointestinal conditions may change its rate or extent.
First-pass metabolism: Drug absorbed from the gut may travel through the portal circulation to the liver before reaching the rest of the body. This can reduce the amount of unchanged drug entering systemic circulation.
Consequently, an oral drug can have delayed or variable even when the same dose is taken.
What affects
Drug does not spread evenly throughout the body after entering systemic circulation. Well-perfused tissues generally receive drug sooner than tissues with lower blood flow.
Movement across tissue barriers depends on membrane permeability and drug properties, including molecular size, lipid solubility, and ionization. Specialized barriers, such as the blood–brain barrier, restrict entry of some drugs.
Drug in blood may be free or reversibly bound to proteins. The free fraction can generally leave the bloodstream and reach tissue sites; bound drug is less available to leave the blood at that moment. Tissue binding or storage can affect where drug accumulates and how long it remains in the body.
Body composition and physiology also influence . Relative amounts of body water and fat, fluid status, and changes in tissue perfusion or barrier function can alter it. For example, a highly lipid-soluble drug may enter fatty tissue, while a drug that binds extensively to plasma proteins may remain more in the bloodstream. These are general tendencies; the pattern is specific to each drug.
Apparent volume of
The apparent volume of () is a calculated measure relating the amount of drug in the body to its concentration in plasma. A relatively small is consistent with more drug remaining in the blood, while a large suggests extensive into tissues.
It is an apparent, not necessarily anatomical, volume. It does not show exactly which tissues contain the drug.