PHARMACOKINETICS-3
METABOLISM
In this post we deal with the third principle of the body's action on the drug administered into it, which is Metabolism or Biotransformation.
Metabolism is the process by which the drug which is a foreign and unwanted substance to the body is biologically converted into another form either to make it inactive, or less toxic and to be eliminated easily. These processes mostly happen in the liver. But unfortunately liver may sometimes biotransform some drugs into more active and highly toxic metabolites unintentionally.
Lipophilic, fat-soluble nonpolar molecules are converted into hydrophilic, water-soluble polar molecules in order to eliminate them from the body.
Metabolism is conducted by two phases of reactions such as Phase-I and Phase-II.
In Phase-I reaction lipophilic, fat-soluble,non-polar molecules are converted into hydrophilic, water-soluble polar molecules by introducing or unmasking a polar group in it. These reactions are occurred mostly by oxidation, reduction(mostly by dehydrogenation, or deprotonation, or removal of a positive charge), and hydrolysis(addition of a water molecule or hydro group).
On the contrary in Phase-II conjugative reaction, conjugation between a functional group of the parent drug and a substrate occurred by a strong covalent bond formation.
Usually the substrate is, Glucuronate(the most common substrate), Acetic Acid, Glutathione(as with the toxic paracetamol metabolite N-acetyl-p-benzoquinone imine in order to make it into inert to save the liver) and sulfate.
Most of the metabolic process occurs in liver but some are in the cellular level. In the tissue, cell metabolism occurs in the endoplasmic reticulum(a cytoplasmic cleft present within the cytoplasm) and in the cytosol.
Factors Affecting Metabolism
Genetic Factors
There are differences between the capacities of metabolizing a drug among individuals. For example, some people are slow acetylation and therefore cannot rapidly inactivate some medicines like isoniazid, procainamide, and hydralazine.
Induction of the Cytochrome P-450 system
Rapid induction of this system increases the rate of metabolism.
and inhibition of this system may block the metabolism of some drugs.
The disease especially of the Liver
Age
Gender
All metabolic processes are mathematically following the zero-order and first-order reactions.
First Order Kinetics
By this model a constant amount of drug is biotransformed in unit time.
For example 10% of a drug,is eliminated or metabolised in the concentration of 100mg/dL by every 2 hrs,then after 2 hours the concentration will be (100-10) 90mg/dL and after 4 hours (90-9),81mg/dL and so on.
The concentration of the drug is directly proportional to the rate of metabolism in first-order kinetics.
Zero Order Kinetics
The amount of drug elimination is a constant figure independent of is the concentration per unit time.
For example if a drug concenration 100mg/dL and the body can remove 10mg/dL in every 2 hour,then after 2 hour there will be a concentration of (100-10)=90mg/dL;and after 4 hours there will be a concentration of (90-10)=80mg/dL and so on.
Alcohol is metabolized as per the zero kinetics only.
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