Physiological factors affecting oral drug absorption

Question 1

The small and large intestine

Answer 1

the biological environments for these intestine differ which causes differences to arise in the absorption

the smaller intestine has a larger surface area making it able to absorb more

the large intestine however is the opposite

Question 2

pH of gastrointestinal fluids

Answer 2

Gastric fluid - 1 - 3.5
Small intestine - 5 - 8
Duodenum - 5 -6
Lower ileum - 8
Large intestine - 8

Gastrointestinal pH may influence drug absorption

the unionised form of a drug in a solution will be absorbed faster than the ionised form

Question 3

Gastric emptying rate

Answer 3

this is the rate at which a drug leaves the stomach and enters the duodenum . Any reduction in this rate is likely to reduce the rate of drug absorption and delay the onset of therapeutic response of the drug

Rate of gastric emptying is also important for drugs which are prone to chemical degradation in stomach by virtue of low pH or enzyme activity associated with gastric fluid.

the longer a drug spends in the stomach the more likely it is to become degraded.

For poorly soluble weak basic drugs administered in a solid dosage form a reduced gastric emptying rate improves bioavailability.

Question 4

Intestinal motility

Answer 4

this is when the drug empties from the stomach and enters small intestine

Propulsive movements are the long rage intestinal contractions.

Mixing movements are the movements of the small intestine in order to increase the area of contact between drug in solution and the gastrointestinal membrane

the greater the intestinal motility the less time it will take for dissolution and drug absorption.

Question 5

Hepatic metabolism

Answer 5

All drugs absorbed from the stomach, small intestine and colon pass into hepatic portal system to liver before reaching systemic circulation.

Liver is the primary site of drug metabolism.

Hence the first pass of absorbed drug through the liver may result in extensive metabolism of drug and significant proportion of absorbed dose of intact drug may never reach systemic circulation.

Question 6

Gastrointestinal secretions

Answer 6

Gastrointestinal secretions secreted in response to presence of food may result in degradation of drugs which are susceptible to chemical hydrolysis or enzymatic metabolism leading to reduction in drug bioavailability.

For stable drugs, gastrointestinal secretions may increase bioavailability by assisting drug dissolution

Bile salts can increase dissolution of poorly soluble drug therefore increasing absorption

Question 7

Increased viscosity of GI contents

Answer 7

Food in the GI tract provides a viscous environment which may result in a reduction of drug dissolution.

an increase in viscosity can reduce rate of diffusion from the lumen to the absorbing membrane line in the GI tract.

Question 8

Food induced changes in blood flow to liver

Answer 8

Increased blood flow to liver will increase the rate at which drugs are presented to the liver. The greater the presentation, the larger the fraction of drugs which escapes the first pass metabolism.

Question 9

Other factors which can affect GI absorption

Answer 9

Local diseases can cause alterations in the gastric pH

Gastric surgery can cause issues with drug absorption