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First-pass metabolism may occur in the liver (for propranolol, lidocaine, clomethiazole, and nitroglycerin) or in the gut (for benzylpenicillin and insulin). [4] The four primary systems that affect the first pass effect of a drug are the enzymes of the gastrointestinal lumen, [5] gastrointestinal wall enzymes, [6] [7] [8] bacterial enzymes [5] and hepatic enzymes.
Drug metabolism is the metabolic breakdown of drugs by living organisms, usually through specialized enzymatic systems. More generally, xenobiotic metabolism (from the Greek xenos "stranger" and biotic "related to living beings") is the set of metabolic pathways that modify the chemical structure of xenobiotics, which are compounds foreign to an organism's normal biochemistry, such as any drug ...
[2] [3] There are two distinct phases in the pathway. The first is the oxidative phase, in which NADPH is generated, and the second is the non-oxidative synthesis of five-carbon sugars. For most organisms, the pentose phosphate pathway takes place in the cytosol; in plants, most steps take place in plastids. [4]
Some textbooks combine the first two phases as the drug is often administered in an active form, which means that there is no liberation phase. Others include a phase that combines distribution, metabolism and excretion into a disposition phase. Other authors include the drug's toxicological aspect in what is known as ADME-Tox or ADMET.
Phosphorylation of glucose is a key reaction in sugar metabolism. The chemical equation for the conversion of D-glucose to D-glucose-6-phosphate in the first step of glycolysis is given by: D-glucose + ATP → D-glucose 6-phosphate + ADP ΔG° = −16.7 kJ/mol (° indicates measurement at standard condition)
Cytochrome P450 oxidases are important enzymes in xenobiotic metabolism.. Xenobiotic metabolism (from the Greek xenos "stranger" and biotic "related to living beings") is the set of metabolic pathways that modify the chemical structure of xenobiotics, which are compounds foreign to an organism's normal biochemistry, such as drugs and poisons.
The model equations follow the principles of mass transport, fluid dynamics, and biochemistry in order to simulate the fate of a substance in the body. [9] Compartments are usually defined by grouping organs or tissues with similar blood perfusion rate and lipid content (i.e. organs for which chemicals' concentration vs. time profiles will be similar).
So, for example, digoxin has a half-life (or t 1 / 2 ) of 24–36 h; this means that a change in the dose will take the best part of a week to take full effect. For this reason, drugs with a long half-life (e.g., amiodarone , elimination t 1 / 2 of about 58 days) are usually started with a loading dose to achieve their desired ...