Advertisement

Topics

Population PK-PD model of pegylated interferon alfa-2a in healthy Korean men.

08:00 EDT 1st September 2018 | BioPortfolio

Summary of "Population PK-PD model of pegylated interferon alfa-2a in healthy Korean men."

Pegylated interferon alfa-2a (PEG-IFN alfa-2a), which was developed to overcome the disadvantages of conventional formulations, is widely prescribed for hepatitis B or C virus infection. It is characterized by pharmacokinetic (PK) and pharmacodynamic (PD) properties much different from those of conventional forms. The present study developed a population PK-PD model of subcutaneous PEG-IFN α-2a in a Korean population. For PK, IFN alfa-2a concentrations were described by a one compartment model with first order absorption, preceded by skin-to-depot first order input. For PD, serum 2'-5' oligoadenylsynthetase (2'-5' OAS) activity was described by an effect compartment model incorporating a tolerance compartment. The baseline serum 2'-5' OAS level was found to have an inverse relationship with sensitivity to tolerance, leading to high tolerance at low baseline. The model revealed that subjects with low baselines experienced time delay, while those with high baselines showed tolerance in their concentration-effect relationships. The developed models matched well with data and simulation results, and the model showed that the optimal dose decreases with the baseline, with no dose effective for a baseline > 250pmol/dl. Our results can serve as a basis for improving dosing regimens of PEG-IFN α-2a in adult patients with chronic hepatitis B or C infection.

Affiliation

Journal Details

This article was published in the following journal.

Name: Journal of pharmaceutical sciences
ISSN: 1520-6017
Pages:

Links

DeepDyve research library

PubMed Articles [21080 Associated PubMed Articles listed on BioPortfolio]

Phase Ib/II Study of Pembrolizumab and Pegylated-Interferon Alfa-2b in Advanced Melanoma.

Objective responses are reported in 34% to 37% of patients with programmed death-1 (PD-1)-naïve advanced melanoma treated with PD-1 inhibitors. Pre-existing CD8+ T-cell infiltrate and interferon (IFN...

HBsAg loss with Pegylated-interferon alfa-2a in hepatitis B patients with partial response to nucleos(t)-ide analog: new switch study.

Hepatitis B surface antigen (HBsAg) loss is seldom achieved with nucleos(t)ide analog (NA) therapy in chronic hepatitis B patients but may be enhanced by switching to finite pegylated-interferon (Peg-...

A highly bioactive Lys-deficient IFN leads to a site-specific di-PEGylated IFN with equivalent bioactivity to that of unmodified IFN-α2b.

Although conjugation with polyethylene glycol (PEGylation) improves the pharmacokinetics of therapeutic proteins, it drastically decreases their bioactivity. Site-specific PEGylation counters the redu...

A minimal physiologically based pharmacokinetic model that predicts anti-PEG IgG-mediated clearance of PEGylated drugs in human and mouse.

Circulating antibodies that specifically bind polyethylene glycol (PEG), a polymer routinely used in protein and nanoparticle therapeutics, have been associated with reduced efficacy and increased adv...

Comparison of topical 5-fluorouracil and interferon alfa-2b as primary treatment modalities for ocular surface squamous neoplasia.

To compare the efficacy of topical 5-fluorouracil 1% (5FU) and interferon alfa-2b 1 MIU/mL (IFN) eye drops as primary treatment modalities for ocular surface squamous neoplasia (OSSN).

Clinical Trials [10529 Associated Clinical Trials listed on BioPortfolio]

Efficacy and Safety of Pegylated Interferon Alfa in Polycythemia Vera

Interferon alfa is an effective treatment of polycythemia vera (PV), but about 20% of patients discontinue their treatment because of side effects and treatment schedule (three times per w...

A Phase II Study of Pegylated Interferon Alfa-2b for the Adjuvant Treatment of Melanoma Subjects in Russia (MK-4031-400)

This study will assess the safety of Pegylated Interferon Alfa-2b (PEG-IFN) as an adjuvant treatment for melanoma.

Safety and Efficacy Study of Pegylated Interferon Lambda With and Without Daclatasvir, Compared to Pegylated Interferon Alfa, Plus Ribavirin in Subjects With Hepatitis C Genotype 2 and 3

The purpose of this study is to determine if 24 weeks of treatment with Pegylated Interferon Lambda plus Ribavirin and 12 weeks of treatment with Pegylated Interferon Lambda plus Ribavirin...

Polyethylene Glycol Interferon Alfa-2b Versus Interferon Alfa-2b in the Treatment of Newly Diagnosed Chronic Myelogenous Leukemia (CML) (C98026/MK-4031-001)

The primary purpose of this study is to compare the efficacy of pegylated interferon alfa-2b (PEG Intron, C98026) versus interferon alfa-2b (Intron® A) in the treatment of participants wi...

Combination Therapy With Pegylated Interferon and Ribavirin in Patients With Chronic Hepatitis C Genotype 2 or 3 Infection Who Previously Have Relapsed After Therapy With Pegylated Interferon and Ribavirin

To evaluate the efficacy of pegylated interferon alfa-2a 40 kD (PEGASYS) combination therapy with ribavirin (Copegus)given for 24 or 48 weeks in patients with chronic hepatitis C (CHC) vir...

Medical and Biotech [MESH] Definitions

A recombinant alfa interferon consisting of 165 amino acids with arginine at positions 23 and 34. It is used extensively as an antiviral and antineoplastic agent.

A recombinant alfa interferon consisting of 165 amino acids with lysine at position 23 and histidine at position 34. It is used extensively as an antiviral and antineoplastic agent.

A recombinant alfa interferon consisting of 165 amino acid residues with arginine in position 23 and histidine in position 34. It is used extensively as an antiviral and antineoplastic agent.

Interferon secreted by leukocytes, fibroblasts, or lymphoblasts in response to viruses or interferon inducers other than mitogens, antigens, or allo-antigens. They include alpha- and beta-interferons (INTERFERON-ALPHA and INTERFERON-BETA).

An interferon regulatory factor that binds upstream TRANSCRIPTIONAL REGULATORY ELEMENTS in the GENES for INTERFERON-ALPHA and INTERFERON-BETA. It functions as a transcriptional activator for the INTERFERON TYPE I genes.

Advertisement
Quick Search
Advertisement
Advertisement

 


DeepDyve research library

Relevant Topics

Gastroenterology
Astroesophageal Reflux Disease (GERD) Barrett's Esophagus Celiac Disease Cholesterol Crohn's Disease Gastroenterology Hepatitis Hepatology Irritable Bowel Syndrome (IBS) Pancreatitis Peptic Ulcer Disease...

Infectious-diseases
Antiretroviral Therapy Clostridium Difficile Ebola HIV & AIDS Infectious Diseases Influenza Malaria Measles Sepsis Swine Flu Tropical Medicine Tuberculosis Infectious diseases are caused by pathogenic...

Wound management
Anything that breaks the skin is a wound because when the skin is broken, there's a risk of germs getting into the body and causing an infection. Follow and track Wound Care News on BioPortfolio: Wound Car...


Searches Linking to this Article