PROTEIN BINDING

Contents

• Protein binding

• Effects of protein binding

• Types of plasma proteins

• Determination of protein binding

• Pharmacokinetic Importance of protein binding

• Disease and protein binding

Intended
learning outcomes

At the end of this
lecture, student will be able to:

• Explain the importance of protein binding of drug
molecules on biological action.

Binding of
drug to proteins may:

• Facilitate the distribution of drugs.

• Inactivate the drug by not enabling a sufficient concentration
at a receptor site

• Retard the excretion of a drug.

The
interaction of drugs to protein may cause:

• Displacement of body hormones or co-administered agent

• Change the configuration of protein to another structure
capable of binding a co-administered agent

• Inactivates the drug biologically by forming a drug-
protein complex

Two Important Plasma Proteins

1. ALBUMIN

2. ACIDGLYCOPROTEIN

ALBUMIN

• Albumin is the most important protein that binds to drug
molecule due to its high concentration compared with other proteins.

• It binds both acidic and basic drugs.

• Constitutes 5% of the total plasma.

∂1-ACIDGLYCOPROTEIN

• Also known as orosomucoid (∂1-globulin)

• Binds to numerous drugs

• Have greater affinity for basic than acidic drugs
molecules

• Binds mostly basic and highly lipophilic drugs.

Things to remember:

• Many drugs bind to the same receptor site but drugs with
higher affinity will replace those drugs with lower affinity by competition.

• Only free and unbound drugs exert therapeutic effect by
interacting with receptors.

Drugs may
bind to protein through:

• Self-Association

• Some drug may self-dissociate to form dimers, trimers or
aggregates of larger size

• Dimers or trimers – is a reaction product of two or three
identical molecules

• May affect solubility, diffusion, transport, therapeutic
action of drugs

Protein
binding is determined by:

• Dialysis

• Ultracentrifugation

• Ultrafiltration

• Sephadex-gel filtration

• Molecular filtration

• Electrophoresis

• Agar plate test

The Pharmacokinetic
Importance of Protein Binding

• Drug-protein binding influences the distribution
equilibrium of the drug

• Plasma proteins exert a buffer and transport function in
the distribution process

• Only free and unbound drug acts can leave the circulatory
system and diffuse into the tissue

Disease and Protein
Binding

• Protein binding will be affected by the presence of
diseases

Drugs showing
Decrease Extent of Protein Binding in the following diseases:

• When drugs bind to protein, Albumin concentration is
reduced

• The exchange of proteins between plasma and interstitial
compartment (normally proceeds at a rate of 5% plasma protein per our) will be
hampered.

• The diffusion of plasma to the interstitial fluid is
increased by:

• Inflammatory process

• Pregnancy

• Use of oral contraceptives

• Diabetes

• Septic shock

• Pulmonary Edema

• The reduced albumin concentration and binding capacity is
due to:

• Change in albumin molecule

• Presence of endogenous binding inhibitors such as free
fatty acids, and metabolic acidosis.

• Hypoalbuminemia may result in patients with cancer, burns,
cardiac failure, cystic fibrosis, enteropathy, inflammations, liver impairment,
malabsorption, nephrotic syndrome, renal failure, sepsis and trauma.

Pathological
Conditions in which Plasma Concentration ∂1 – ACIDGLYCOPROTEIN is increased

Displacement of Drugs
from their Plasma Protein Binding by Other Drugs given concomitantly

SUMMARY

• Albumin is the most important protein that binds to drug
molecule due to its high concentration compared with other proteins

• It binds both acidic and basic and constitute 5% of the
total plasma

• ∂1-acidglycoprotein also known as orosomucoid
(∂1-globulin) and binds to numerous drugs

• Have greater affinity for basic than acidic drugs
molecules Binds only basic and highly lipophilic drugs

• Effects of protein binding and its pharmacokinetic importance
is studied.