What are the factors affecting protein drug binding?
What are the factors affecting protein drug binding?
Putting in a nutshell, all factors, especially drug interactions and patient related factors that affect protein or tissue binding of drugs, influence: Pharmacokinetics of drugs: A decrease in plasma protein-drug binding i.e. an increase in unbound drug concentration, favours tissue redistribution and/or clearance of …
What is plasma protein binding?
Albumin
Albumin and α-1-acid glycoprotein are the two plasma proteins that are involved in protein binding.
How can plasma protein binding be reduced?
Equilibrium dialysis is the most widely accepted method for assessing plasma protein binding as non specific binding effects are minimised compared with other methods such as ultrafiltration, but is a relatively slow process, from 4-24 hours at 37 C.
What conditions can decrease protein binding?
Plasma protein binding may decrease in renal disease due to uremia, hypoalbuminemia, or due to drug interactions. Decreased plasma protein binding leads to an increase in free plasma fraction causing an increase in volume of distribution and a shorter elimination half life.
How does plasma protein binding affect drug distribution?
Protein-binding may affect drug activity in one of two ways: either by changing the effective concentration of the drug at its site of action or by changing the rate at which the drug is eliminated, thus affecting the length of time for which effective concentrations are maintained.
Does plasma protein binding affect bioavailability?
It can limit the bioavailability of active compounds by controlling their passage through biological membranes; however, binding to plasma proteins allows hydrophobic drugs to be transported in the aqueous environment of the human organism.
Why is plasma protein binding important?
Plasma proteins, by virtue of their high concentration, control the free drug concentration in plasma and in compartments in equilibrium with plasma, thereby, effectively attenuating drug potency in vivo.
What are the limitations of higher plasma protein binding?
7.1. High plasma protein binding limits the partitioning of xenobiotics from the blood into the tissues where they could be metabolized. This serves to extend the half-life of the xenobiotic as only free chemical may enter the metabolizing enzymes.
How does plasma protein binding affect bioavailability?
What is the effect of protein binding on drugs quizlet?
Proteins are large molecules that cannot exit the circulation (unless the person is quite ill), so drugs bound to large molecules cannot exit the circulation the way free (unbound) drug can. This means that only free drug can be active.
How do changes in protein binding affect drug concentration?
Increasing the concentration of blood proteins lowers the DC, i.e. decreases the free drug concentration (Figure 2b). On the other hand, a decrease of blood proteins can influence the drug’s side-effects [1]. In this situation, correction of drug dosage is needed.
How does protein binding affect absorption?
Extensive plasma protein binding will increase the amount of drug that has to be absorbed before effective therapeutic levels of unbound drug are reached. For example, acidic dugs (such as acetyl salicylic acid – aspirin) are often substantially bound to albumin. Elimination of a highly bound drug may be delayed.
What are the factors affecting plasma protein binding of drugs?
Plasma protein binding of a drug means the ability/affinity of a drug to bind to proteins in plasma, namely albumin and certain glycoproteins. As far as the factors that affect protein binding go, they are very non specific and as such we cannot make any generalisations.
How is plasma protein binding related to half life?
High plasma protein binding may also have an impact on efficacy since it is usually the free fraction of drug that is responsible for the pharmacological action. Half-life can be related to the Volume of distribution using the following equation
How does the pH of a drug affect its binding?
The physiologic pH determines the presence of active anionic and cationic groups on the albumin molecules to bind to a variety of drugs. Concentration of Protein/Binding ComponentsAmong the plasma proteins, binding predominantly occurs with albumin as it is present in a higher concentration in comparison to other plasma proteins.
What happens when a compound is bound to a protein?
Compounds that are extensively bound to plasma proteins will have a low Volume of distribution (Vdss), can have long plasma half-lives (T1/2), and have low clearance (Cl) by both liver (hepatic) and kidney (Renal) routes.
