22 Questions
The method is based on the rate of disappearance of ______ from a dialysis cell.
drug
A ______ dialysis bag containing the drug-protein solution is suspended in the buffer solution.
cellophane
The dialysis process follows the rate law: -d[Dt]/dt = k______.
Df
______ bonding is actually not bond formation at all, but rather the tendency of hydrophobic molecules or hydrophobic parts of molecules to avoid water.
hydrophobic
Large hydrophobic species such as proteins avoid the water molecules in an ______ solution by associating into micelle-like structures.
aqueous
Both the solutions are stirred continuously and are periodically removed from outside the dialysis bag and analyzed ______.
spectrophotometrically
Albumin is the most important plasma protein due to its _______________ concentration relative to other proteins.
high
The interaction between a protein and a drug molecule can be represented as P + D → _______________.
PD
The association constant 'k' is the ratio of the concentration of _______________ to the product of the concentrations of unbound protein and unbound drug.
protein-drug complex
α1-acid glycoprotein is a plasma protein that has a greater affinity for _______________ drugs.
basic
Protein binding can _______________ the distribution of the drug throughout the body.
facilitate
One of the experimental methods for determining protein binding is _______________.
equilibrium dialysis
Protein binding can also _______________ the excretion of a drug which may accumulate in the body.
retard
Protein binding can lead to a _______________ change in the protein which may become capable of binding other agents.
configurational
The solubility behavior of a drug is studied in the ______________ of a protein.
presence
The effect of protein on the partitioning behavior of drug molecules between an aqueous and an organic solvent that are ______________.
immiscible
In equilibrium dialysis method, the protein solution is enclosed within a ______________ membrane.
semipermeable
The ultrafiltration method is similar to equilibrium dialysis method, but uses ______________ to force the solvent and the free drug across the membrane.
hydraulic pressure or centrifugation
Dynamic dialysis is a ______________ method for studying the concentration of bound drug in protein solution.
kinetic
Equilibrium dialysis method is used to assess the degree of binding by measuring the conc. of free and ______________ drug.
bounded
In equilibrium dialysis method, the solution is agitated slightly until ______________ has been achieved.
equilibrium
Ultrafiltration method is more convenient than other methods for routine determinations because it is less ______________ consuming.
time
Study Notes
Equilibrium Dialysis Method
- The method is based on the rate of disappearance of a drug from a dialysis cell, which is proportional to the concentration of unbound drug.
- The apparatus consists of a jacketed (temperature-controlled) beaker with a buffer solution, a cellophane dialysis bag containing a drug-protein solution, and continuous stirring.
- The dialysis process follows the rate law: -d[Dt]/dt = k[Df], where [Dt] is the total drug concentration, [Df] is the concentration of free or unbound drug, and k is the first-order rate constant representative of the diffusion process.
Hydrophobic Interaction
- Hydrophobic bonding is not a bond formation, but rather the tendency of hydrophobic molecules or hydrophobic parts of molecules to avoid water.
- Large hydrophobic species, such as proteins, avoid water molecules in an aqueous solution by associating into micelle-like structures with non-polar portions in contact in the inner regions and polar ends facing the water molecules.
Protein Binding
- Plasma proteins, such as albumin, globulin, and lipoproteins, can bind with a large number of drug molecules, altering the biological properties of the drug.
- Protein binding can:
- Facilitate the distribution of the drug throughout the body
- Inactivate a drug by reducing the concentration of free drug at the receptor site
- Retard the excretion of a drug, leading to accumulation in the body
- Alter the duration of action of a drug
- Displace body hormones or co-administered agents
- Bring about a configurational change in the protein, which may bind other agents
- Alter the therapeutic effect by forming a drug-protein complex that is biologically active
Albumin Binding
- Albumin is the most important plasma protein due to its high concentration and ability to bind both acidic and basic drugs.
Tetracycline-Albumin Binding
- Another plasma protein is α1-acid glycoprotein, which binds to numerous drugs, with a greater affinity for basic than acidic drugs.
Binding Equilibria
- The interaction between a protein (P) and a drug molecule (D) can be represented as: P + Df ⇌ PD
- The association constant (K) is: K = [PD] / [P] [Df]
- [PD] is the concentration of the protein-drug complex, [P] is the concentration of unbound protein, and [Df] is the concentration of unbound drug.
Experimental Methods for Determining Protein Binding
- Equilibrium dialysis method
- Ultrafiltration method
- Dynamic dialysis method
- Other methods: electrophoresis, gel filtration, and NMR
- These methods can be used to:
- Study the solubility behavior of a drug in the presence and absence of a protein
- Investigate the effect of protein on the partitioning behavior of drug molecules between an aqueous and an organic solvent
- Analyze the change in spectral characteristics of drug molecules for assessing the degree of binding
This method determines the rate of drug-protein binding through a dialysis process. It involves a jacketed beaker with a buffer solution and a cellophane dialysis bag containing the drug-protein solution.
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