Drug absorption

Drug absorption

Before drugs can be clinically effective, they must be absorbed.  Absorption is the process of a drug moving from its site of delivery into the bloodstream. The chemical composition of a drug, as well as the environment into which a drug is placed, work together to determine the rate and extent of drug absorption.  

Introduction to Drug Absorption

Absorption is the process of delivering a drug into the blood stream.  Absorption can be accomplished by administering the drug in a variety of different ways (e.g. orally, rectally, intra-muscularly, subcutaneously, inhalation, topically, etc.).  Note, that if a drug is administered intravenously (placed directly into the blood stream), the need for absorption is bypassed entirely.

For drug absorption to occur, a drug must cross biologic barriers (e.g. epithelial/endothelial cells, etc.).  Only a few drugs move across cellular barriers in an “active” way; that is, a way that requires energy (ATP) and moves the drug from an area of low concentration to an area of higher concentration.    On the other hand, most drugs cross cellular barriers via passive diffusion; that is, drugs simply move from an area of higher concentration to an area of lower concentration by diffusing through cell membranes.  This type of drug movement does not require any energy expenditure, but will be influenced by the size of the drug and the solubility of the drug.  

For drug absorption to be most efficient, the properties of the drug itself and the pH of the environment where the drug is located must be considered.  Most drugs are either weak acids or weak bases.  Drugs that are weak acids will pick up a proton when placed in an acidic environment and will, thus, be un-ionized.

H+ + A- <-> HA

In the above example, when the weak acid, A-, is placed into an acidic environment, H+; the drug picks up a proton and is no longer ionized (it becomes protonated as HA).  If the same acid, A-, is placed into an alkaline environment, -OH, the drug will remain ionized, as A-.

Drugs that are un-ionized will be better able to diffuse through a lipid cellular membrane, cross a biologic barrier, and enter the bloodstream (e.g. be absorbed) compared to drugs that are ionized.  Thus, a key take-home point is:  a drug that is a weak acid will be best absorbed in an acidic environment (because it gains a proton and becomes un-ionized).

The opposite is true for drugs that are weak bases.  Consider, a weak base, NH3. In an acidic environment, H+, the drug gains a proton and becomes ionized.  

H+ + NH3 <-> NH4+

On the other hand, in an alkaline environment, a drug that is a weak base would remain un-ionized.  

Thus, the take-home message, again, is that weakly basic drugs are more likely to absorbed in alkaline environments where they remain un-ionized compared to acidic environments where whey gain a proton and pick up a charge.  Ionized (or charged) drugs are not absorbed as efficiently as un-ionized drugs are.  Practically speaking, this means that if taken orally, a drug that is a weak acid will be absorbed primarily in the acidic environment; whereas, a drug that is a weak base will be absorbed in the alkaline environment small intestines.  

Physiogically speaking, even though the stomach is acidic, it is not well-suited for drug absorption, even for drugs that are weak acids due to its thick mucus layer and relatively small surface area. The stomach is more of a “storage” organ than an absorptive one.   In contrast, the small intestines have a large surface area available for absorption owing to extensive villi and microvilli.  As a result, acidic drugs are most likely to be absorbed in the acidic areas of the proximal duodenum; whereas, basic drugs will be best absorbed in more alkaline areas of the distal ileum.

In addition to a drug’s ionization status, a drug is more likely to be absorbed if it contains lipophillic chemical groups, lacks bulky/oxygenated side chains, and is not too large in size.

Other factors that also impact drug absorption include the following:

  1. Physiologically, a drug’s absorption is enhanced if there is a large surface area available for absorption (e.g. villi/microvilli of intestinal tract) and if there is a large blood supply for the drug to move down its concentration gradient.
  2. The presence of food/other medications in the stomach may impact drug absorption – sometimes enhancing absorption and other times forming insoluble complexes that are not absorbed (it depends on the specific drug).
  3. Some drugs are inactivated before they can be absorbed by enzymes, acidity, bacteria, etc.

This three page article is a good introduction into absorption and administration of drugs. The article summarizes the different processes of absorption including passive diffusion, facilitated passive diffusion, active transport and pinocytosis. Summaries of oral and parenteral administration, and controlled-release forms are mentioned as well.

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Absorption is the process of delivering a drug into the blood stream.  Absorption can be accomplished by administering the drug in a variety of different ways (e.g. orally, rectally, intra-muscularly, subcutaneously, inhalation, topically, etc.).  Note, that if a drug is administered intravenously (placed directly into the blood stream), the need for absorption is bypassed entirely.

For drug absorption to occur, a drug must cross biologic barriers (e.g. epithelial/endothelial cells, etc.).  Only a few drugs move across cellular barriers in an “active” way; that is, a way that requires energy (ATP) and moves the drug from an area of low concentration to an area of higher concentration.    On the other hand, most drugs cross cellular barriers via passive diffusion; that is, drugs simply move from an area of higher concentration to an area of lower concentration by diffusing through cell membranes.  This type of drug movement does not require any energy expenditure, but will be influenced by the size of the drug and the solubility of the drug.  

For drug absorption to be most efficient, the properties of the drug itself and the pH of the environment where the drug is located must be considered.  Most drugs are either weak acids or weak bases.  Drugs that are weak acids will pick up a proton when placed in an acidic environment and will, thus, be un-ionized.

H+ + A- <-> HA

In the above example, when the weak acid, A-, is placed into an acidic environment, H+; the drug picks up a proton and is no longer ionized (it becomes protonated as HA).  If the same acid, A-, is placed into an alkaline environment, -OH, the drug will remain ionized, as A-.

Drugs that are un-ionized will be better able to diffuse through a lipid cellular membrane, cross a biologic barrier, and enter the bloodstream (e.g. be absorbed) compared to drugs that are ionized.  Thus, a key take-home point is:  a drug that is a weak acid will be best absorbed in an acidic environment (because it gains a proton and becomes un-ionized).

The opposite is true for drugs that are weak bases.  Consider, a weak base, NH3. In an acidic environment, H+, the drug gains a proton and becomes ionized.  

H+ + NH3 <-> NH4+

On the other hand, in an alkaline environment, a drug that is a weak base would remain un-ionized.  

Thus, the take-home message, again, is that weakly basic drugs are more likely to absorbed in alkaline environments where they remain un-ionized compared to acidic environments where whey gain a proton and pick up a charge.  Ionized (or charged) drugs are not absorbed as efficiently as un-ionized drugs are.  Practically speaking, this means that if taken orally, a drug that is a weak acid will be absorbed primarily in the acidic environment; whereas, a drug that is a weak base will be absorbed in the alkaline environment small intestines.  

Physiogically speaking, even though the stomach is acidic, it is not well-suited for drug absorption, even for drugs that are weak acids due to its thick mucus layer and relatively small surface area. The stomach is more of a “storage” organ than an absorptive one.   In contrast, the small intestines have a large surface area available for absorption owing to extensive villi and microvilli.  As a result, acidic drugs are most likely to be absorbed in the acidic areas of the proximal duodenum; whereas, basic drugs will be best absorbed in more alkaline areas of the distal ileum.

In addition to a drug’s ionization status, a drug is more likely to be absorbed if it contains lipophillic chemical groups, lacks bulky/oxygenated side chains, and is not too large in size.

Other factors that also impact drug absorption include the following:

  1. Physiologically, a drug’s absorption is enhanced if there is a large surface area available for absorption (e.g. villi/microvilli of intestinal tract) and if there is a large blood supply for the drug to move down its concentration gradient.
  2. The presence of food/other medications in the stomach may impact drug absorption – sometimes enhancing absorption and other times forming insoluble complexes that are not absorbed (it depends on the specific drug).
  3. Some drugs are inactivated before they can be absorbed by enzymes, acidity, bacteria, etc.

The 1.5 minute long video depicts the fate of drugs that are administered orally including first-pass metabolism, entero-hepatic recycling, and the effects of GI contents on absorption.

Average: 2.3 (3 votes)

Absorption is the process of delivering a drug into the blood stream.  Absorption can be accomplished by administering the drug in a variety of different ways (e.g. orally, rectally, intra-muscularly, subcutaneously, inhalation, topically, etc.).  Note, that if a drug is administered intravenously (placed directly into the blood stream), the need for absorption is bypassed entirely.

For drug absorption to occur, a drug must cross biologic barriers (e.g. epithelial/endothelial cells, etc.).  Only a few drugs move across cellular barriers in an “active” way; that is, a way that requires energy (ATP) and moves the drug from an area of low concentration to an area of higher concentration.    On the other hand, most drugs cross cellular barriers via passive diffusion; that is, drugs simply move from an area of higher concentration to an area of lower concentration by diffusing through cell membranes.  This type of drug movement does not require any energy expenditure, but will be influenced by the size of the drug and the solubility of the drug.  

For drug absorption to be most efficient, the properties of the drug itself and the pH of the environment where the drug is located must be considered.  Most drugs are either weak acids or weak bases.  Drugs that are weak acids will pick up a proton when placed in an acidic environment and will, thus, be un-ionized.

H+ + A- <-> HA

In the above example, when the weak acid, A-, is placed into an acidic environment, H+; the drug picks up a proton and is no longer ionized (it becomes protonated as HA).  If the same acid, A-, is placed into an alkaline environment, -OH, the drug will remain ionized, as A-.

Drugs that are un-ionized will be better able to diffuse through a lipid cellular membrane, cross a biologic barrier, and enter the bloodstream (e.g. be absorbed) compared to drugs that are ionized.  Thus, a key take-home point is:  a drug that is a weak acid will be best absorbed in an acidic environment (because it gains a proton and becomes un-ionized).

The opposite is true for drugs that are weak bases.  Consider, a weak base, NH3. In an acidic environment, H+, the drug gains a proton and becomes ionized.  

H+ + NH3 <-> NH4+

On the other hand, in an alkaline environment, a drug that is a weak base would remain un-ionized.  

Thus, the take-home message, again, is that weakly basic drugs are more likely to absorbed in alkaline environments where they remain un-ionized compared to acidic environments where whey gain a proton and pick up a charge.  Ionized (or charged) drugs are not absorbed as efficiently as un-ionized drugs are.  Practically speaking, this means that if taken orally, a drug that is a weak acid will be absorbed primarily in the acidic environment; whereas, a drug that is a weak base will be absorbed in the alkaline environment small intestines.  

Physiogically speaking, even though the stomach is acidic, it is not well-suited for drug absorption, even for drugs that are weak acids due to its thick mucus layer and relatively small surface area. The stomach is more of a “storage” organ than an absorptive one.   In contrast, the small intestines have a large surface area available for absorption owing to extensive villi and microvilli.  As a result, acidic drugs are most likely to be absorbed in the acidic areas of the proximal duodenum; whereas, basic drugs will be best absorbed in more alkaline areas of the distal ileum.

In addition to a drug’s ionization status, a drug is more likely to be absorbed if it contains lipophillic chemical groups, lacks bulky/oxygenated side chains, and is not too large in size.

Other factors that also impact drug absorption include the following:

  1. Physiologically, a drug’s absorption is enhanced if there is a large surface area available for absorption (e.g. villi/microvilli of intestinal tract) and if there is a large blood supply for the drug to move down its concentration gradient.
  2. The presence of food/other medications in the stomach may impact drug absorption – sometimes enhancing absorption and other times forming insoluble complexes that are not absorbed (it depends on the specific drug).
  3. Some drugs are inactivated before they can be absorbed by enzymes, acidity, bacteria, etc.

This simulation allows learners to apply the Henderson-Hasselbach equation to calculate percent ionization of a drug based upon its chemical properties (e.g. pKa) and the surrounding environment.  There is a calculator where learners can enter their own pKa and pH values as well as two practice problems with answers.

Average: 2 (1 vote)

Absorption is the process of delivering a drug into the blood stream.  Absorption can be accomplished by administering the drug in a variety of different ways (e.g. orally, rectally, intra-muscularly, subcutaneously, inhalation, topically, etc.).  Note, that if a drug is administered intravenously (placed directly into the blood stream), the need for absorption is bypassed entirely.

For drug absorption to occur, a drug must cross biologic barriers (e.g. epithelial/endothelial cells, etc.).  Only a few drugs move across cellular barriers in an “active” way; that is, a way that requires energy (ATP) and moves the drug from an area of low concentration to an area of higher concentration.    On the other hand, most drugs cross cellular barriers via passive diffusion; that is, drugs simply move from an area of higher concentration to an area of lower concentration by diffusing through cell membranes.  This type of drug movement does not require any energy expenditure, but will be influenced by the size of the drug and the solubility of the drug.  

For drug absorption to be most efficient, the properties of the drug itself and the pH of the environment where the drug is located must be considered.  Most drugs are either weak acids or weak bases.  Drugs that are weak acids will pick up a proton when placed in an acidic environment and will, thus, be un-ionized.

H+ + A- <-> HA

In the above example, when the weak acid, A-, is placed into an acidic environment, H+; the drug picks up a proton and is no longer ionized (it becomes protonated as HA).  If the same acid, A-, is placed into an alkaline environment, -OH, the drug will remain ionized, as A-.

Drugs that are un-ionized will be better able to diffuse through a lipid cellular membrane, cross a biologic barrier, and enter the bloodstream (e.g. be absorbed) compared to drugs that are ionized.  Thus, a key take-home point is:  a drug that is a weak acid will be best absorbed in an acidic environment (because it gains a proton and becomes un-ionized).

The opposite is true for drugs that are weak bases.  Consider, a weak base, NH3. In an acidic environment, H+, the drug gains a proton and becomes ionized.  

H+ + NH3 <-> NH4+

On the other hand, in an alkaline environment, a drug that is a weak base would remain un-ionized.  

Thus, the take-home message, again, is that weakly basic drugs are more likely to absorbed in alkaline environments where they remain un-ionized compared to acidic environments where whey gain a proton and pick up a charge.  Ionized (or charged) drugs are not absorbed as efficiently as un-ionized drugs are.  Practically speaking, this means that if taken orally, a drug that is a weak acid will be absorbed primarily in the acidic environment; whereas, a drug that is a weak base will be absorbed in the alkaline environment small intestines.  

Physiogically speaking, even though the stomach is acidic, it is not well-suited for drug absorption, even for drugs that are weak acids due to its thick mucus layer and relatively small surface area. The stomach is more of a “storage” organ than an absorptive one.   In contrast, the small intestines have a large surface area available for absorption owing to extensive villi and microvilli.  As a result, acidic drugs are most likely to be absorbed in the acidic areas of the proximal duodenum; whereas, basic drugs will be best absorbed in more alkaline areas of the distal ileum.

In addition to a drug’s ionization status, a drug is more likely to be absorbed if it contains lipophillic chemical groups, lacks bulky/oxygenated side chains, and is not too large in size.

Other factors that also impact drug absorption include the following:

  1. Physiologically, a drug’s absorption is enhanced if there is a large surface area available for absorption (e.g. villi/microvilli of intestinal tract) and if there is a large blood supply for the drug to move down its concentration gradient.
  2. The presence of food/other medications in the stomach may impact drug absorption – sometimes enhancing absorption and other times forming insoluble complexes that are not absorbed (it depends on the specific drug).
  3. Some drugs are inactivated before they can be absorbed by enzymes, acidity, bacteria, etc.

This set of 52 slides described principles and processes of drug absorption, the impact of pH and pKa on drug ionization, and bioavailability and first pass metabolism.

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