Pharmacokinetics: Drug Absorption, Bioavailability and Bioequivalence
Drug Absorption and Bioavailability – Explained Simply
When you take a medicine, it needs to reach your bloodstream to start working. This process is called absorption. It is how a drug moves from where it is given (like your mouth, skin, or muscle) into the blood. The amount of drug that gets absorbed and how fast this happens are both very important in determining how well the drug works.
If a drug is given directly into a vein (intravenous or IV), it goes straight into the blood, so absorption isn’t a concern. However, a medicine must cross bodily barriers to get to the bloodstream when it is administered topically, injected into a muscle, or eaten orally. Several things can affect how well this process happens.
Factors That Affect Absorption
1. Water Solubility
Drugs that come in solid form, like tablets or capsules, must dissolve in water in your body before they can be absorbed. If a drug doesn’t dissolve easily in water (such as aspirin or griseofulvin), it will be absorbed more slowly. Some drugs like ketoconazole dissolve only in acidic conditions, so stomach acid helps in their absorption.
Drugs in liquid form are absorbed faster than solids or oily preparations because they are already dissolved. So, liquid medicines often work quicker.
2. Drug Concentration
Drugs move through membranes more easily when there is a higher concentration on one side than the other. A more concentrated drug solution is absorbed faster than a diluted one, especially when the drug is absorbed by passive diffusion.
3. Surface Area
The larger the surface area available for absorption, the faster it happens. The small intestine, with its many folds and finger-like structures called villi, has a large surface area, making it an ideal place for drug absorption.
4. Blood Flow
Good blood flow at the absorption site helps move the drug into the bloodstream and maintains a difference in concentration that drives absorption. For example, applying heat or exercising increases blood flow and speeds up absorption. On the other hand, using drugs that narrow blood vessels, like adrenaline, can slow it down.
Absorption by Different Routes
1. Oral (By Mouth)
When drugs are taken orally, they must pass through the stomach and intestinal lining to reach the bloodstream. These linings are fatty, so drugs that are fat-soluble and not charged pass through more easily.
- Acidic drugs like aspirin are absorbed in the stomach because they are mostly uncharged there.
- Basic drugs like morphine are absorbed in the intestine, where they become less charged.
Even though acidic drugs can be absorbed in the stomach, the process is slow because the stomach lining is thick and the surface area is small. The small intestine absorbs drugs faster because of its large surface area.
The presence of food can slow down drug absorption by diluting the drug, slowing stomach emptying, or forming complexes that the body cannot absorb well (e.g. tetracyclines with milk). However, some drugs, like lumefantrine, are absorbed better when taken with fatty food.
Some drugs are destroyed in the stomach or intestine. For example, penicillin G is broken down by stomach acid, and insulin is broken down by digestive enzymes, making them ineffective when taken by mouth. To solve this, we can use enteric-coated tablets that resist stomach acid or sustained-release forms that dissolve slowly.
A protein called P-glycoprotein (P-gp) in the gut can pump some absorbed drugs back into the intestine, lowering their overall absorption. Drugs like digoxin and cyclosporine are affected by this. Some drugs, like quinidine or verapamil, can block this protein and increase absorption, while others, like rifampin, can enhance its activity and reduce absorption.
Other medications taken at the same time can also interfere. For example, antacids can bind with tetracycline and stop it from being absorbed. Antibiotics may disturb gut bacteria that are needed for recycling some drugs like birth control pills.
2. Subcutaneous (Under the Skin) and Intramuscular (Into Muscle)
When drugs are injected under the skin or into the muscle, they are placed near blood vessels. Fat-soluble drugs pass through capillary walls easily. Water-soluble or larger molecules may be absorbed through gaps or via the lymph system.
Muscle injections usually lead to faster and more predictable absorption than skin injections. Heat and exercise can help by increasing blood flow. Vasoconstrictors like adrenaline can slow absorption if we want the drug to stay longer at the injection site. Some drugs are made into long-acting forms called depot preparations, such as benzathine penicillin or depot contraceptives, which slowly release the drug.
3. Topical (On Skin, Eyes, or Mucous Membranes)
Some drugs can be absorbed through the skin, especially if they are fat-soluble. Only a few drugs can do this well, like nicotine, fentanyl, or hormone patches. Skin absorption increases if the drug is rubbed in or covered, which keeps the skin moist and improves penetration.
Damaged or broken skin absorbs drugs more easily. For example, tannic acid applied on burned skin has caused liver damage. Drugs placed in the eye, like timolol drops, can enter the bloodstream and cause side effects such as slow heart rate. Drugs can also be absorbed through mucous membranes like the mouth, rectum, or vagina.
Bioavailability
Bioavailability means how much of the drug actually reaches the blood in its active form. When a drug is injected into a vein, its bioavailability is 100%. However, when taken by mouth, bioavailability may be lower because:
- The drug might not be fully absorbed.
- Some of it might be broken down by the stomach, intestines, or liver before reaching the blood (called first-pass metabolism).
Even with injections, some drug may stay at the site and not enter the bloodstream completely.
Bioequivalence
Two drug products are said to be bioequivalent if they deliver the same amount of drug into the blood at the same rate. Different tablets of the same drug may contain the same amount of the ingredient, but differences in how they are made can affect how the drug is released and absorbed.
A drug must first break apart (disintegrate) and then dissolve before it is absorbed. Things like particle size, type of tablet, and added ingredients can affect this. Poorly soluble drugs like aspirin or griseofulvin may absorb better when their particles are very small.
Bioavailability differences are especially important for drugs with a narrow safety range, such as digoxin or blood thinners. Even small changes in absorption can lead to serious problems. However, for most drugs, small differences between brands don’t matter much.
References
Latest Editions of
- Rang H. P., Dale M. M., Ritter J. M., Flower R. J., Rang and Dale’s Pharmacology,.Churchil Livingstone Elsevier
- K.D.Tripathi. Essentials of Medical Pharmacology, JAYPEE Brothers Medical Publishers (P) Ltd, New Delhi.
- Sharma H. L., Sharma K. K., Principles of Pharmacology, Paras medical publisher