The main component of gastric juice is gastric acid, with a pH of about 1 to 3. After gastric juice reaches the duodenum, it is neutralized by bicarbonate in the pancreatic juice, which increases the pH. The small intestine itself secretes weak alkaline liquid, with a pH of about 6 to 7. The intestinal fluid secreted by the mucus of large intestine makes the pH higher.

Different pH environments in the digestive tract determine the dissociation state between weak acidic drugs and weak alkaline drugs. Molecular drugs are easier to absorb than ionic drugs.

Gastrointestinal fluid contains enzymes, bile salts, mucin and other substances, which have different effects on drug absorption. Mucus becomes a barrier to diffusion and absorption of drugs, especially high-fat drugs

Gastric emptying

Gastric airspeed

Inherent movement of the small intestine

The inherent movement of the intestine can promote further disintegration of the solid preparation, allowing it to be fully mixed with the intestinal fluid to dissolve, increasing the contact between the drug and the surface of the absorbing mucosa, which is conducive to the absorption of the drug.

Some drugs can affect the speed of the intestines and interfere with the absorption of other drugs

Delay or reduce the absorption of drugs

Promote the absorption of drugs

Various digestive enzymes and enzymes produced by intestinal bacteria clusters exist in the digestive tract mucosa, which can cause metabolic reactions to become inactive before the drug is absorbed, and has a certain or even a great impact on the efficacy of the drug.

When the membrane permeability rate of a drug is less than the blood flow rate, membrane permeability is a rate-limiting step of absorption

When the membrane permeability rate of the drug is greater than the blood flow rate, blood flow is a speed limiting step for absorption

The blood flow decreases, and the ability of the absorption site to transport drugs is reduced. It cannot maintain a high concentration difference of drugs - that is, leakage state, and the absorption of drugs is extremely high.

definition

The greater the effect of liver first pass, the more the drug is metabolized, the lower the blood concentration of the prototype drug, and the significantly lower the efficacy of the drug.

definition

mechanism

Example

measure

Performance

Lymph system transport plays an important role in the absorption of macromolecular drugs

Drugs absorbed through the lymphatic system do not pass through the liver and have no liver first effect

Lymph system transport has important clinical significance for the absorption of drugs that are susceptible to metabolism in the liver and the absorption and transport of some anti-cancer directed lymph system.

For weak acid or weak alkaline drugs, due to the influence of gastrointestinal pH, the drug exists in two forms: undissociated and dissociated. The proportion of the two is determined by the dissociation constant PKa of the drug and the pH value of the absorption site.

Undissociated molecules with high lipid solubleness are prone to pass through the lipid-like membrane of epithelial cells, while the dissociated ionic type is not easy to pass and is difficult to absorb.

PH-Distribution Theory

Usually, the large oil/water partition coefficient of the drug indicates that the drug has good fat solubility and high absorption rate.

The molecular weight of a drug is also related to absorption

The absorption of active transport drugs is not related to drug fat solubility

Dissolution rate

Oral preparations administered in solid state must be dissolved in gastrointestinal solutions before absorption. Insoluble drugs or drugs with very slow dissolution rates often become the rate limiting stage during the absorption process.

Penicillin is very easy to hydrolyze, so it is not suitable for oral use and is designed as a powder needle for injection.

Nitroglycerin is prone to hydrolysis and failure, so it should be designed as a sublingual drug administration preparation and a non-aqueous vehicle injection agent.

Omeprazole is unstable in water, so it should be designed as an enteric-coated preparation and a lyophilized agent for injection.

Insulin is easily inactive by gastrointestinal digestive enzymes to break the ring, and is not easily absorbed, so it is designed as an injection agent.