A FELSZIVODAS ES A METABOLIZMUS SZEREPE A GYOGYSZEREK HATASMODJABAN

Translated title of the contribution: The role of absorption and metabolism of drugs in their mode of action

Research output: Contribution to journalArticle

Abstract

Drug effect requires the presence of an adequate drug concentration in the fluid bathing the target tissue. In the translocation of drugs their absorption and distribution play an essential role. Absorption is defined as the passage of drugs from their sites of administration into the plasma, while distribution means the transport of drugs from the circulation to tissues. In general, drugs during absorption and distribution should pass across biological membranes rich in lipid constituents. The intensity of absorption is determined partly by the chemical composition of the membrane and partly by the physico-chemical properties of the drugs. Non-polar substances dissolve freely in non-polar solvent such as lipids and therefore penetrate cell membranes freely by passive diffusion in the direction of the concentration gradient. Passive diffusion ('down-hill' transport) is the most frequent and important process playing role in absorption, but other mechanisms with less importance are also involved (carrier mediated transport, active transport, ion-pair formation, pinocytosis). Most frequently the drugs are administered orally. In this case weak acids are absorbed right from the stomach, while weak bases just from the intestine. Drugs absorbed from the gastrointestinal tract are transported by the portal vein to the liver, where they can be metabolised before entering the systemic circulation ('first-pass' metabolism). To escape 'first-pass' metabolism different routes of drug administrations are advisable sublingual, transdermal). Absorption can be characterised by the plasma concentration-time curve from which the most important parameters can be calculated (AUC(0-∞); t(max); C(max); t( 1/4 ); MRT; α; β). The area under the plasma concentration-time curve (AUC) presents that portion of the dose which is biologically available for the pharmacological effect (bioavailability). The term bioavailability is also used to indicate the unchanged and changed portions of the drug separately that pass into the systemic circulation after oral administration. Drugs are foreign to the body from which the organism should be cleared. Drug elimination is preceded by the metabolism. Metabolic alteration of drugs involves two kinds of biochemical reactions which often occur sequentially, known as phase I and as phase II reactions. Metabolic conversion of drugs usually inactivates them and increases their polarity, which helps their excretion. Nevertheless, products of phase I reactions are sometimes more active and rarely more toxic or carcinogenic than the parent compound. Phase II reactions (conjugation) normally results in inactive compounds. Drug metabolism takes place mainly in the liver, but extrahepatic tissues are also involved in the process. Microsomal enzymes, mainly cytochrome P-450, play the key role in drug conversions. Cytochrome P-450 can be induced by drugs, pesticides or food additives. The induction can multiply the intensity of drug metabolism of the patients treated with drugs having inductive capacity. Some drugs can inhibit the metabolism of other drugs. Interactions of drugs are based mainly by induction or inhibition of their metabolism. The better knowledge of drug absorption and metabolism suggest ways to construct drug preparations with more advantageous properties concerning their effectiveness, onset, duration of effect, including elimination.

Original languageHungarian
Pages (from-to)771-781
Number of pages11
JournalGyogyszereszet
Volume40
Issue number11
Publication statusPublished - 1996

Fingerprint

Pharmaceutical Preparations
Cytochrome P-450 Enzyme System
Biological Availability
Area Under Curve
Sublingual Administration
Drug Administration Routes
Pinocytosis
Lipids
Food Additives
Drug Compounding
Membranes
Poisons
Liver
Ion Transport
Portal Vein
Foreign Bodies
Drug Interactions
Pesticides
Intestines
Oral Administration

ASJC Scopus subject areas

  • Pharmacology

Cite this

A FELSZIVODAS ES A METABOLIZMUS SZEREPE A GYOGYSZEREK HATASMODJABAN. / Magyar, K.

In: Gyogyszereszet, Vol. 40, No. 11, 1996, p. 771-781.

Research output: Contribution to journalArticle

@article{7e7c469d72f24037ae8334bbeb4c66a3,
title = "A FELSZIVODAS ES A METABOLIZMUS SZEREPE A GYOGYSZEREK HATASMODJABAN",
abstract = "Drug effect requires the presence of an adequate drug concentration in the fluid bathing the target tissue. In the translocation of drugs their absorption and distribution play an essential role. Absorption is defined as the passage of drugs from their sites of administration into the plasma, while distribution means the transport of drugs from the circulation to tissues. In general, drugs during absorption and distribution should pass across biological membranes rich in lipid constituents. The intensity of absorption is determined partly by the chemical composition of the membrane and partly by the physico-chemical properties of the drugs. Non-polar substances dissolve freely in non-polar solvent such as lipids and therefore penetrate cell membranes freely by passive diffusion in the direction of the concentration gradient. Passive diffusion ('down-hill' transport) is the most frequent and important process playing role in absorption, but other mechanisms with less importance are also involved (carrier mediated transport, active transport, ion-pair formation, pinocytosis). Most frequently the drugs are administered orally. In this case weak acids are absorbed right from the stomach, while weak bases just from the intestine. Drugs absorbed from the gastrointestinal tract are transported by the portal vein to the liver, where they can be metabolised before entering the systemic circulation ('first-pass' metabolism). To escape 'first-pass' metabolism different routes of drug administrations are advisable sublingual, transdermal). Absorption can be characterised by the plasma concentration-time curve from which the most important parameters can be calculated (AUC(0-∞); t(max); C(max); t( 1/4 ); MRT; α; β). The area under the plasma concentration-time curve (AUC) presents that portion of the dose which is biologically available for the pharmacological effect (bioavailability). The term bioavailability is also used to indicate the unchanged and changed portions of the drug separately that pass into the systemic circulation after oral administration. Drugs are foreign to the body from which the organism should be cleared. Drug elimination is preceded by the metabolism. Metabolic alteration of drugs involves two kinds of biochemical reactions which often occur sequentially, known as phase I and as phase II reactions. Metabolic conversion of drugs usually inactivates them and increases their polarity, which helps their excretion. Nevertheless, products of phase I reactions are sometimes more active and rarely more toxic or carcinogenic than the parent compound. Phase II reactions (conjugation) normally results in inactive compounds. Drug metabolism takes place mainly in the liver, but extrahepatic tissues are also involved in the process. Microsomal enzymes, mainly cytochrome P-450, play the key role in drug conversions. Cytochrome P-450 can be induced by drugs, pesticides or food additives. The induction can multiply the intensity of drug metabolism of the patients treated with drugs having inductive capacity. Some drugs can inhibit the metabolism of other drugs. Interactions of drugs are based mainly by induction or inhibition of their metabolism. The better knowledge of drug absorption and metabolism suggest ways to construct drug preparations with more advantageous properties concerning their effectiveness, onset, duration of effect, including elimination.",
author = "K. Magyar",
year = "1996",
language = "Hungarian",
volume = "40",
pages = "771--781",
journal = "Gyogyszereszet",
issn = "0017-6036",
publisher = "Magyar Gyogyszereszeti Tarsasag",
number = "11",

}

TY - JOUR

T1 - A FELSZIVODAS ES A METABOLIZMUS SZEREPE A GYOGYSZEREK HATASMODJABAN

AU - Magyar, K.

PY - 1996

Y1 - 1996

N2 - Drug effect requires the presence of an adequate drug concentration in the fluid bathing the target tissue. In the translocation of drugs their absorption and distribution play an essential role. Absorption is defined as the passage of drugs from their sites of administration into the plasma, while distribution means the transport of drugs from the circulation to tissues. In general, drugs during absorption and distribution should pass across biological membranes rich in lipid constituents. The intensity of absorption is determined partly by the chemical composition of the membrane and partly by the physico-chemical properties of the drugs. Non-polar substances dissolve freely in non-polar solvent such as lipids and therefore penetrate cell membranes freely by passive diffusion in the direction of the concentration gradient. Passive diffusion ('down-hill' transport) is the most frequent and important process playing role in absorption, but other mechanisms with less importance are also involved (carrier mediated transport, active transport, ion-pair formation, pinocytosis). Most frequently the drugs are administered orally. In this case weak acids are absorbed right from the stomach, while weak bases just from the intestine. Drugs absorbed from the gastrointestinal tract are transported by the portal vein to the liver, where they can be metabolised before entering the systemic circulation ('first-pass' metabolism). To escape 'first-pass' metabolism different routes of drug administrations are advisable sublingual, transdermal). Absorption can be characterised by the plasma concentration-time curve from which the most important parameters can be calculated (AUC(0-∞); t(max); C(max); t( 1/4 ); MRT; α; β). The area under the plasma concentration-time curve (AUC) presents that portion of the dose which is biologically available for the pharmacological effect (bioavailability). The term bioavailability is also used to indicate the unchanged and changed portions of the drug separately that pass into the systemic circulation after oral administration. Drugs are foreign to the body from which the organism should be cleared. Drug elimination is preceded by the metabolism. Metabolic alteration of drugs involves two kinds of biochemical reactions which often occur sequentially, known as phase I and as phase II reactions. Metabolic conversion of drugs usually inactivates them and increases their polarity, which helps their excretion. Nevertheless, products of phase I reactions are sometimes more active and rarely more toxic or carcinogenic than the parent compound. Phase II reactions (conjugation) normally results in inactive compounds. Drug metabolism takes place mainly in the liver, but extrahepatic tissues are also involved in the process. Microsomal enzymes, mainly cytochrome P-450, play the key role in drug conversions. Cytochrome P-450 can be induced by drugs, pesticides or food additives. The induction can multiply the intensity of drug metabolism of the patients treated with drugs having inductive capacity. Some drugs can inhibit the metabolism of other drugs. Interactions of drugs are based mainly by induction or inhibition of their metabolism. The better knowledge of drug absorption and metabolism suggest ways to construct drug preparations with more advantageous properties concerning their effectiveness, onset, duration of effect, including elimination.

AB - Drug effect requires the presence of an adequate drug concentration in the fluid bathing the target tissue. In the translocation of drugs their absorption and distribution play an essential role. Absorption is defined as the passage of drugs from their sites of administration into the plasma, while distribution means the transport of drugs from the circulation to tissues. In general, drugs during absorption and distribution should pass across biological membranes rich in lipid constituents. The intensity of absorption is determined partly by the chemical composition of the membrane and partly by the physico-chemical properties of the drugs. Non-polar substances dissolve freely in non-polar solvent such as lipids and therefore penetrate cell membranes freely by passive diffusion in the direction of the concentration gradient. Passive diffusion ('down-hill' transport) is the most frequent and important process playing role in absorption, but other mechanisms with less importance are also involved (carrier mediated transport, active transport, ion-pair formation, pinocytosis). Most frequently the drugs are administered orally. In this case weak acids are absorbed right from the stomach, while weak bases just from the intestine. Drugs absorbed from the gastrointestinal tract are transported by the portal vein to the liver, where they can be metabolised before entering the systemic circulation ('first-pass' metabolism). To escape 'first-pass' metabolism different routes of drug administrations are advisable sublingual, transdermal). Absorption can be characterised by the plasma concentration-time curve from which the most important parameters can be calculated (AUC(0-∞); t(max); C(max); t( 1/4 ); MRT; α; β). The area under the plasma concentration-time curve (AUC) presents that portion of the dose which is biologically available for the pharmacological effect (bioavailability). The term bioavailability is also used to indicate the unchanged and changed portions of the drug separately that pass into the systemic circulation after oral administration. Drugs are foreign to the body from which the organism should be cleared. Drug elimination is preceded by the metabolism. Metabolic alteration of drugs involves two kinds of biochemical reactions which often occur sequentially, known as phase I and as phase II reactions. Metabolic conversion of drugs usually inactivates them and increases their polarity, which helps their excretion. Nevertheless, products of phase I reactions are sometimes more active and rarely more toxic or carcinogenic than the parent compound. Phase II reactions (conjugation) normally results in inactive compounds. Drug metabolism takes place mainly in the liver, but extrahepatic tissues are also involved in the process. Microsomal enzymes, mainly cytochrome P-450, play the key role in drug conversions. Cytochrome P-450 can be induced by drugs, pesticides or food additives. The induction can multiply the intensity of drug metabolism of the patients treated with drugs having inductive capacity. Some drugs can inhibit the metabolism of other drugs. Interactions of drugs are based mainly by induction or inhibition of their metabolism. The better knowledge of drug absorption and metabolism suggest ways to construct drug preparations with more advantageous properties concerning their effectiveness, onset, duration of effect, including elimination.

UR - http://www.scopus.com/inward/record.url?scp=0030476581&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=0030476581&partnerID=8YFLogxK

M3 - Article

AN - SCOPUS:0030476581

VL - 40

SP - 771

EP - 781

JO - Gyogyszereszet

JF - Gyogyszereszet

SN - 0017-6036

IS - 11

ER -