Crossing the gut wall

A swallowed tablet is not "in" the body yet. The inside of your gut is technically still outside: it is a long tube that runs through you. To act, the drug must dissolve in the gut fluid and then cross the wall of the gut into the blood. That is absorption.

Most absorption happens in the small intestine, not the stomach. The small intestine's lining is folded into ridges, covered in finger-like villi, and each villus cell has even tinier microvilli. These folds give a surface area of the order of tens of square metres, many times the area of your skin. (The Human Body lab shows the digestive system in detail.)

What decides whether a drug crosses?

• Solubility. It has to dissolve first. The tablet's coating and fillers control how fast it breaks up.
• Size and charge. The gut wall is made of cells wrapped in a fatty membrane. Small, fat-soluble (lipophilic) molecules slip through easily. Large or electrically charged molecules cross poorly.
• Time in the gut. Food slows stomach emptying, so a drug reaches the intestine later. Food can also bind to a drug or change the acidity, so it can raise absorption for some drugs and lower it for others. That is why a leaflet may say "with food" or "on an empty stomach": the maker has measured what happens.
• Release rate. Coatings and special designs can make a tablet release its drug slowly (World 2).

Bioavailability, again: F = AUC(oral) / AUC(IV). Suppose Drug A gives an AUC of 40 units·h/L when given by mouth and 100 units·h/L when the same dose is given into a vein (fictional numbers). Then F = 40 / 100 = 0.4: only 40% of the swallowed dose reaches the circulation. The other 60% was never absorbed or was removed on the way (next lesson).

A common wrong idea is that tablets are absorbed through the stomach lining. A few small molecules cross a little there, but for most drugs the small intestine is where the action is.