Phharmacokinetic,(Absorption)

Pharmacokinetics

Kinetics refers to movement. Pharmacokinetics deals with a drug’s actions as it moves through the body. Therefore, pharmacokinetics discusses how a drug is:

• absorbed (taken into the body)
• distributed (moved into various tissues)
• metabolized (changed into a form that can be excreted)
• excreted (removed from the body).

This branch of pharmacology is also concerned with a drug’s onset of action, peak concentration level, and duration of action.

Absorption

Drug absorption covers a drug’s progress from the time it’s administered, through its passage to the tissues, until it reaches systemic circulation.

On a cellular level, drugs are absorbed by several means’primarily through active or passive transport.

Passive Transport

Passive transport requires no cellular energy because diffusion allows the drug to move from an area of higher concentration to one of lower concentration. Passive transport occurs when small molecules diffuse across membranes and stops when drug concentration on both sides of the membrane is equal.

Active Transport

Active transport requires cellular energy to move the drug from an area of lower concentration to one of higher concentration. Active transport is used to absorb electrolytes, such as sodium and potassium, as well as some drugs such as levodopa.

Taking a bite

Pinocytosis is a unique form of active transport that occurs when a cell engulfs a drug particle. Pinocytosis is commonly employed to transport fat-soluble vitamins (vitamins A, D, E, and K).

Watch the speed limit!

If only a few cells separate the active drug from the systemic circulation, absorption will occur rapidly and the drug will quickly reach therapeutic levels in the body. Typically, absorption occurs within seconds or minutes when a drug is administered sublingually, I.V., or by inhalation.

Not so fast

Absorption occurs at a slower rate when drugs are administered by the oral, I.M., or subQ routes because the complex membrane systems of GI mucosal layers, muscle, and skin delay drug passage.

At a snail’s pace

At the slowest absorption rates, drugs can take several hours or days to reach peak concentration levels. A slow rate usually occurs with rectally administered or sustained-release drugs.

Not enough time

Other factors can affect how quickly a drug is absorbed. For example, most absorption of oral drugs occurs in the small intestine. If a patient has had large sections of the small intestine surgically removed, drug absorption decreases because of the reduced surface area and the reduced time that the drug is in the intestine.

Look to the liver

Drugs absorbed by the small intestine are transported to the liver before being circulated to the rest of the body. The liver may metabolize much of the drug before it enters the circulation. This mechanism is referred to as the first-pass effect. Liver metabolism may inactivate the drug; if so, the first-pass effect lowers the amount of active drug released into the systemic circulation. Therefore, higher drug dosages must be administered to achieve the desired effect.

More blood, more absorption

Increased blood flow to an absorption site improves drug absorption, whereas reduced blood flow decreases absorption. More rapid absorption leads to a quicker onset of drug action.

For example, the muscle area selected for I.M. administration can make a difference in the drug absorption rate. Blood flows faster through the deltoid muscle (in the upper arm) than through the gluteal muscle (in the buttocks). The gluteal muscle, however, can accommodate a larger volume of drug than the deltoid muscle.

Slowed by pain and stress

Pain and stress can decrease the amount of drug absorbed. This may be due to a change in blood flow, reduced movement through the GI tract, or gastric retention triggered by the autonomic nervous system response to pain.

High fat doesn’t help

High-fat meals and solid foods slow the rate at which contents leave the stomach and enter the intestines, delaying intestinal absorption of a drug.

Dosage form factors

Drug formulation (such as tablets, capsules, liquids, sustained-release formulas, inactive ingredients, and coatings) affects the drug absorption rate and the time needed to reach peak blood concentration levels.

Absorption increase or decrease?

Combining one drug with another drug, or with food, can cause interactions that increase or decrease drug absorption, depending on the substances involved.