The pKa of weakly acidic and strongly basic drugs is the PH value of drugs when they are ionized at 50% in solution, and each drug has its fixed pKa value. When the difference from pH value increases or decreases mathematically, the ratio of ionic to nonionic concentration of drugs changes exponentially. In pharmacokinetics, the ion barrier phenomenon is characterized by "less acid is easy to be acidic, and acid-base is difficult".
The explanation is that "acid is less and easy" weakly acidic drugs dissociate less in acidic body fluids and easily penetrate cell membranes; "Acid-base-inseparable" weakly acidic drugs dissociate more in alkaline body fluids, so it is difficult to penetrate the cell membrane. For example, barbiturate poisoning caused by weakly acidic drugs can be treated with sodium bicarbonate to alkalize blood and urine, promote the transfer of drugs from brain tissue to plasma, and accelerate the excretion of drugs from urine, which can be used to rescue drug poisoning.
Main factors affecting drug absorption through passive transport;
1, fat-soluble: Fat-soluble drugs can be dissolved in lipids in biofilm and spread, so they are easily absorbed. Water-soluble drugs are not easily absorbed by passive diffusion, but are easily absorbed by active transport mechanisms, such as transporters. For example, water-soluble β -lactam antibiotics are easily absorbed because they can be actively transported through the gastrointestinal tract PEPT 1 transporter.
2. Dissociation degree, pH value in liquid environment: Weak acid drugs have high dissociation degree in alkaline environment and are not easily absorbed. Therefore, in case of weak acid drug poisoning, urine should be alkalized with weak alkaline drugs to reduce the reabsorption of weak acid drugs and promote their excretion and detoxification. The pH value of liquid environment is closely related to the degree of drug dissociation.
3. Molecular weight: Absorption is related to the molecular weight of the drug. Water-soluble drugs with large molecular weight are not easily absorbed, while water-soluble drugs with small molecular weight can be freely absorbed through the membrane pores of biofilm. High molecular weight, although a fat-soluble drug, has limited absorption.
4. Concentration difference between the two sides of the membrane: the greater the concentration difference, the more conducive to diffusion.
5. Permeability of the membrane.