(Presseportal openBroadcast) - The metabolism of drugs in the body is generally carried out under the catalytic action of the enzyme. P450 enzyme in live is the mainly enzyme involved in drug pharmacokinetics in the body. The most important characteristic of P450 enzyme is that it can be induced or inhibited. At the same time, there are significant differences in race, age and sex, and the P450 enzyme has obvious polymorphism. Those effects will affect the content and activity of the enzyme so as to make the effect on the drug efficiency and the pharmacokinetics behavior. The following are the main factors that influence the pharmacokinetics of the drug:
When two or more than two kinds of drugs are used, there will be an interaction between drugs. Some drugs such as phenobarbital, carbamazepine, phenytoin sodium or rifampicin can increase the activity of P450 enzyme, accelerating the metabolism of other drugs to weaken the efficacy of drugs. Some drugs such as chloramphenicol, allopurinol, isoniazid and ketoconazole can inhibit P450 enzyme, slowing down the metabolism of drugs. Pharmacokinetics among drugs is generally considered to be a potential hazard and should be avoided. Liver microsomal technique can be used to study the potential metabolic interactions between drugs in vitro.
The expression of P450 in different species of animals and human bodies has the quality and quantity differences, so the CYP450 enzyme substrate&product from different species of animal and human body and P450 activity are different. Therefore, this will inevitably lead to their different efficacy and toxicities from different races.
Age and gender differences
Age differences in drug pharmacokinetics are mainly in children and the elderly. Children are in the growth and development of the body that the liver is not yet fully developed, so the content and activity of the liver drug enzyme is low, and the drug pharmacokinetics in the body will be impacted. The elderly are the opposite.
There is no obvious sex difference in the metabolism of most drugs in the human body, but there are some differences in the in vivo process of some drugs. For example: the half-life of lidocaine in the female body is longer than that of male; plasma concentration of aspirin and rifampicin in females is higher than that of males.
Genetic variability is one of the main reasons for the differences in drug pharmacokinetics. Because many enzymes(such as P450, methyl transferase) involved in drug pharmacokinetics have genetic variability. The genetic phenotype appears to be strong metabolic type and weak metabolic type.
Liver is the main metabolic organ of drugs, so when the liver function is affected, the liver metabolism of the drug is bound to be significantly affected.
Now, in order to support the development of pharmacokinetics, researchers will be involved in the pharmacokinetic service for clinical assessment and data delivery.
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