What Is Drug Absorption?
Drug absorption is the amount of compound that enters the body from the site of administration. In general, drug absorption can potentially occur via multiple routes (for example the lungs and skin) depending on the drug’s biopharmaceutical properties. However, this post will focus on enteral drug absorption and how drugs enter the gastrointestinal tract after oral administration. The enteral absorption of a molecule can help you determine if it can be developed into a successful therapeutic oral drug.
Drugs in gastric fluids
After taking a medicine with food or a glass of water, the drug moves from the mouth via the throat to enter the stomach where it comes into contact with gastric fluids. In practice, a very small amount of drug can be absorbed from the stomach. This is because the stomach is designed to act as a receptacle or reservoir but it’s not intended for absorption. Even small molecules like ethanol do not get absorbed much through the stomach. Drug absorption occurs largely in the intestines. However, it’s still important to understand how much drug dissolves in gastric fluids. This is because the dissolved drug can then be presented in a readily absorbed form as the gastric fluid is transferred into the intestines.
Transformation of gastric fluids to intestinal fluids
The stomach transfers gastric fluid which may contain ingested food or liquid into the small intestine. As the drug in stomach fluid enters the small intestine, it’s mixed with biliary fluids to form intestinal fluids. In the fed state, the transferred gastric fluids are mixed with a lot more biliary fluid in comparison to the fasting state. This typically raises the pH of the fluid and exposes the drug to biliary surfactants which can sharply increase drug dissolution in vivo.
Drugs are absorbed from intestinal fluid
Drugs are mostly absorbed into the intestines from intestinal fluids. How much and how fast a drug dissolves in the gastrointestinal fluids determines how the drug can enter into the absorptive surfaces of the intestine. The amount of drug that stays dissolved in the gastric fluid or can dissolve or re-dissolve in the intestinal fluid has the potential to be absorbed.
Absorption and bioavailability are not the same
Absorption is related to bioavailability because drugs that are orally bioavailable have to be absorbed. However, absorption is not the same as bioavailability. Oral bioavailability is the amount of drug after oral administration that reaches the systemic circulation of the body (so the amount of drug in the blood after (possible) metabolism in the gut wall and passage through the liver). A drug may be 100% absorbed but have very low bioavailability because it is metabolised in the liver for example. This is the case with drugs that have a high first pass effect such as nitroglycerin and propanolol.
Biorelevant media and absorption
In vitro biorelevant media simulate the in vivo stomach and intestinal fluids in the fasted or fed state. Therefore in vitro dissolution results in biorelevant media are essential to understand in vivo solubility and dissolution processes that occur when a drug contacts gastrointestinal fluid after a meal (with food) or a glass of water (without food). These in vitro dissolution results enable developers to match release profiles of their test (bioequivalent) formulation to the reference formulation or to optimise a formulation of an insoluble drug to improve absorption. If coupled with biotransformation data such as metabolism in the gut and liver, distribution and excretion the dissolution results can be used to predict a drug’s bioavailability.