The main difference between peginterferon alfa 2a and 2b is the structure of the polyethylene glycol (PEG) chain and the resulting effects. That is; Peginterferon-alfa-2a ( PEG-IFN alfa-2a ) contains a branched 40 kDa PEG chain. And this chain is covalently bound to the lysine residues of interferon-alpha-2a via stable amide bonds and therefore circulates as an intact molecule. However, peginterferon-alfa-2b ( PEG-IFN alfa-2b ) contains a linear 12 kDa PEG chain. The chain is primarily covalently bound to histidine-34 of interferon-alpha-2b via an unstable urethane bond, which is subjected to hydrolysis after the injection and thus releases native interferon-alpha-2b.
Peginterferon-alfa-2a and -2b are the two types of pegylated interferons that are widely used to treat chronic hepatitis C (HCV) infection . However, peginterferon-alpha-2a has a very limited volume of distribution, longer half-life and reduced clearance and can therefore be administered once a week regardless of body weight. However, peginterferon-alpha-2b has a shorter half-life in serum and therefore requires body weight-based dosing. In addition, peginterferon-alfa-2a has a relatively constant absorption and is mainly distributed in the blood and organs, while peginterferon-alfa-2b has both rapid absorption and wider distribution in the body.
Key areas covered
1. What is peginterferon Alfa 2A - definition, structure, properties 2. What is peginterferon Alfa 2B - definition, structure, properties 3. What are the similarities between peginterferon Alfa 2A and 2B - overview of the common characteristics 4. What is the difference between peginterferon Alfa 2A and 2B - comparison of the main differences
Chronic hepatitis C infection, interferon, peginterferon-alfa-2A, peginterferon-alfa-2B, PEG chain
What is Peginterferon Alfa 2A
Peginterferon-alfa-2a ( PEG-IFN-alfa-2a ) is a form of monopegylated interferon with a 40 kDa branched PEG unit. It consists of 4 major positional isomers involving Lys31, Lys121, Lys131 and Lys134 of interferon alfa-2a. In addition, the PEG unit is attached via stable amide bonds. Therefore, peginterferon-alfa-2a exists as an intact molecule in the circulation. As such, it gets a longer half-life.
In addition, it shows a lower clearance compared to the native peginterferon-alfa-2a. Peginterferon-alfa-2a can be given once a week, regardless of body weight. It also has a restricted volume distribution; in the blood and organs.
What is Peginterferon Alfa 2B
Peginterferon-alfa-2b ( PEG-IFN-alfa-2b ) is the second form of monopegylated interferon with a 12 kDa linear PEG unit covalently attached to the His34 residue. It also has 14 major positional isomers. The attachment of the PEG chain, however, takes place through an unstable urethane bond, which is subject to hydrolysis after the injection and thus releases native interferon-alpha-2b.
For this reason, p eginterferon-alpha-2b has a shorter half-life in serum and requires a dose that is dependent on body weight. In addition, peginterferon alfa-2b is more widely distributed in the body.
Similarities Between Peginterferon Alfa 2A and 2B
- Peginterferon-alfa-2a and 2b are the two types of pegylated interferons that are widely used to treat chronic hepatitis C (HCV) infection.
- They are the modified forms of interferon, a A drug that mimics a protein in the body that the immune system uses to destroy viruses.
- They contain a covalently bound polyethylene glycol (PEG) unit, which leads to differences in the immunological, pharmacokinetic and, in turn, in their pharmacodynamic properties.
- PEG is an inert molecule that reduces the breakdown of protein, when crosslinked, whereas the biological activity of proteins is preserved.
- Nevertheless, PEGs consist of monomeric ethylene glycols that are linked together to form complex chains. This in turn creates enormous diversity in the chains of PEG by linking ethylene glycols in different lengths and with different branching patterns.
- They also differ in size depending on the type of PEG chain attached to the interferon .
- The general recommendation for the treatment of patients with chronic hepatitis C is combination therapy with PEG-IFN (alfa-2a or alfa-2b) and ribavirin (RBV). Here ribavirin or tribavirin is an antiviral drug used to treat RSV infections, some hemorrhagic fevers, and hepatitis C. It usually helps to maximize response rates in infected patients.
- For hepatitis B, they are given alone.
- Basically, you avoid the highly fluctuating serum concentrations and the cumbersome dosage regimes associated with conventional interferon alfa.
- In addition , they significantly increase the sustained virological response rates compared to the standard interferons .
- However , they have similar efficacy as alfa-2a and alfa-2b in terms of sustained virological response rate .
Difference between peginterferon Alfa 2A and 2B
Peginterferon-alfa-2a refers to a form of the recombinant drug with a branched 40 kDa PEG chain that is covalently linked to the interferon via stable amide bonds at lysine residues. On the other hand, peginterferon-alfa-2b refers to the other form of recombinant drug with a 12 kDa linear PEG chain that is mainly covalently linked to histidine-34 of interferon.
The trade name for peginterferon-alfa-2a is Pegasys, while the trade name for peginterferon-alfa-2b is Pegatron .
Size and structure of the PEG chains
Peginterferon-alfa-2a contains a 40 kDa branched PEG chain, but peginterferon-alfa-2b contains a 12- kDa linear PEG chain.
Attachment points of PEG chains
Peginterferon-alfa-2a contains the PEG chain which is either bound to Lys31, Lys121, Lys131 or Lys134 and thus forms positional isomers. However, peginterferon-alfa-2b contains the PEG chain attached to His34.
Peginterferon-alfa-2a circulates as an intact molecule, but peginterferon-alfa-2b has an unstable urethane bond that hydrolyzes after injection, releasing native interferon-alpha-2b.
Half a life
Peginterferon-alfa-2a has a longer half-life than peginterferon-alfa-2b.
Peginterferon-alfa-2a can be administered once a week regardless of body weight. However, peginterferon alfa-2b requires dosing based on body weight.
Admission and distribution
Peginterferon-alfa-2a has a relatively constant absorption and is mainly distributed in the blood and organs, but peginterferon-alfa-2b is both rapidly absorbed and more widely distributed in the body.
Peginterferon-alfa-2a is one of the two forms of modified interferons that are important in the treatment of HCV. Generally, it contains a branched, 40 kDa PEG chain that is covalently linked to the lysine residues of the interferon. Thus, an essential feature of it is the stability, which supports the circulation of the peginterferon-alfa-2a as an intact molecule. Hence, it has a longer half-life. For this reason, it can be given once a week regardless of body weight. In contrast, peginterferon-alfa-2b is the other form of modified interferon that is used to treat HCV. However, it contains a linear chain of 12 kDa PEG chain covalently linked to His34. It is also subject to hydrolysis and therefore peginterferon-alfa-2b has a shorter half-life. This requires a dose that is dependent on body weight. Therefore, the main difference between peginterferon-alfa-2a and 2b is the way in which the PEG chain is attached and how it works.
1. Foster, Graham R. “Pegylated Interferons for the Treatment of Chronic Hepatitis C: Pharmacological and Clinical Differences Between Peginterferon-Alpha-2a and Peginterferon-Alpha-2b.” Drugs , US National Library of Medicine, 2010, Available here.
1. "Peginterferon alfa-2a" by Fallaner - The pegylation of IFNs on His-34 improves antiviral activity in vitro via the JAK / STAT route (Public Domain) via Commons Wikimedia 2. "Peginterferon alfa-2b" by Fallaner - Pegylating IFNs at His-34 enhance in vitro antiviral activity via the JAK / STAT pathway (Public Domain) via Commons Wikimedia