Skip to main content
Key Specialties
Cardiology Diabetology Endocrinology Gastroenterology Geriatrics and Gerontology Gynecology and Obstetrics Hematology Infectious Disease Internal Medicine Nephrology Neurology Oncology Pediatrics Respiratory Medicine Rheumatology Surgery
Congress Coverage
2024 ACC Congress 2023 ESMO Congress 2023 EASD Congress 2023 ERS Congress 2023 ESC Congress
Clinical Collections
Advances in Alzheimer’s

At a glance: The STEP trials

A round-up of the STEP phase 3 clinical trials evaluating semaglutide for weight loss in people with overweight or obesity.
ADVANCED SEARCH
Log in
Top
Clinical Pharmacokinetics
Published in: Clinical Pharmacokinetics 11/2017

01-11-2017 | Original Research Article

A Bayesian Approach for Population Pharmacokinetic Modeling of Pegylated Interferon α-2a in Hepatitis C Patients

Author: Mohammad I. Saleh

Published in: Clinical Pharmacokinetics | Issue 11/2017

Login to get access

Abstract

Background

Pegylated interferon α-2a (PEG-IFN-α-2a) is an antiviral drug used for the treatment of chronic hepatitis C virus (HCV) infection. This study describes the population pharmacokinetics of PEG-IFN-α-2a in hepatitis C patients using a Bayesian approach. A possible association between patient characteristics and pharmacokinetic parameters is also explored.

Methods

A Bayesian population pharmacokinetic modeling approach, using WinBUGS version 1.4.3, was applied to a cohort of patients (n = 292) with chronic HCV infection. Data were obtained from two phase III studies sponsored by Hoffmann-La Roche. Demographic and clinical information were evaluated as possible predictors of pharmacokinetic parameters during model development.

Results

A one-compartment model with an additive error best fitted the data, and a total of 2271 PEG-IFN-α-2a measurements from 292 subjects were analyzed using the proposed population pharmacokinetic model. Sex was identified as a predictor of PEG-IFN-α-2a clearance, and hemoglobin baseline level was identified as a predictor of PEG-IFN-α-2a volume of distribution.

Conclusion

A population pharmacokinetic model of PEG-IFN-α-2a in patients with chronic HCV infection was presented in this study. The proposed model can be used to optimize PEG-IFN-α-2a dosing in patients with chronic HCV infection. Optimal PEG-IFN-α-2a selection is important to maximize response and/or to avoid potential side effects such as thrombocytopenia and neutropenia.

Clinical Trials Registration Numbers

NV15942 and NV15801.
Literature
1.
Shepard CW, Finelli L, Alter MJ. Global epidemiology of hepatitis C virus infection. Lancet Infect Dis. 2005;5(9):558–67.CrossRefPubMed
2.
Prieto M, Berenguer M, Rayon JM, Cordoba J, Arguello L, Carrasco D, et al. High incidence of allograft cirrhosis in hepatitis C virus genotype 1b infection following transplantation: relationship with rejection episodes. Hepatology. 1999;29(1):250–6.CrossRefPubMed
3.
Forman LM, Lewis JD, Berlin JA, Feldman HI, Lucey MR. The association between hepatitis C infection and survival after orthotopic liver transplantation. Gastroenterology. 2002;122(4):889–96.CrossRefPubMed
4.
American Association for the Study of Liver Diseases, Infectious Diseases Society of America. HCV guidance: recommendations for testing, managing, and treating hepatitis C. 2015. http://​www.​hcvguidelines.​org. Accessed 26 Feb 2016.
5.
6.
Bailon P, Palleroni A, Schaffer CA, Spence CL, Fung WJ, Porter JE, et al. Rational design of a potent, long-lasting form of interferon: a 40 kDa branched polyethylene glycol-conjugated interferon alpha-2a for the treatment of hepatitis C. Bioconj Chem. 2001;12(2):195–202.CrossRef
7.
Fried MW, Shiffman ML, Reddy KR, Smith C, Marinos G, Goncales FL Jr, et al. Peginterferon alfa-2a plus ribavirin for chronic hepatitis C virus infection. N Engl J Med. 2002;347(13):975–82.CrossRefPubMed
8.
Bruno R, Sacchi P, Ciappina V, Zochetti C, Patruno S, Maiocchi L, et al. Viral dynamics and pharmacokinetics of peginterferon alpha-2a and peginterferon alpha-2b in naive patients with chronic hepatitis c: a randomized, controlled study. Antivir Ther. 2004;9(4):491–7.PubMed
9.
Bressler B, Wang K, Grippo JF, Heathcote EJ. Pharmacokinetics and response of obese patients with chronic hepatitis C treated with different doses of PEG-IFN alpha-2a (40KD) (PEGASYS). Br J Clin Pharmacol. 2009;67(3):280–7.CrossRefPubMedPubMedCentral
10.
Diago M, Crespo J, Olveira A, Perez R, Barcena R, Sanchez-Tapias JM, et al. Clinical trial: pharmacodynamics and pharmacokinetics of re-treatment with fixed-dose induction of peginterferon alpha-2a in hepatitis C virus genotype 1 true non-responder patients. Aliment Pharmacol Ther. 2007;26(8):1131–8.CrossRefPubMed
11.
Hadziyannis SJ, Sette H Jr, Morgan TR, Balan V, Diago M, Marcellin P, et al. Peginterferon-alpha2a and ribavirin combination therapy in chronic hepatitis C: a randomized study of treatment duration and ribavirin dose. Ann Intern Med. 2004;140(5):346–55.CrossRefPubMed
12.
Spiegelhalter DJ, Best NG, Carlin BP, Van Der Linde A. Bayesian measures of model complexity and fit. J R Stat Soc Ser B Stat Methodol. 2002;64(4):583–639.CrossRef
13.
Xu C, Gupta S, Krishna G, Cutler D, Wirth S, Galoppo C, et al. Population pharmacokinetics of peginterferon alfa-2b in pediatric patients with chronic hepatitis C. Eur J Clin Pharmacol. 2013;69(12):2045–54.CrossRefPubMed
14.
Harris JM, Martin NE, Modi M. Pegylation: a novel process for modifying pharmacokinetics. Clin Pharmacokinet. 2001;40(7):539–51.CrossRefPubMed
15.
Di Bisceglie AM, Fan X, Chambers T, Strinko J. Pharmacokinetics, pharmacodynamics, and hepatitis C viral kinetics during antiviral therapy: the null responder. J Med Virol. 2006;78(4):446–51.CrossRefPubMed
16.
Silva M, Poo J, Wagner F, Jackson M, Cutler D, Grace M, et al. A randomised trial to compare the pharmacokinetic, pharmacodynamic, and antiviral effects of peginterferon alfa-2b and peginterferon alfa-2a in patients with chronic hepatitis C (COMPARE). J Hepatol. 2006;45(2):204–13.CrossRefPubMed
17.
Gelman A, Carlin JB, Stern HS, Rubin DB. Bayesian data analysis. Boca Raton: Chapman & Hall/CRC; 2014.
18.
Kaplan D. Bayesian statistics for the social sciences. In: Little T, editor. Methodology in the social sciences series. 1st ed. New York: Guilford Publications; 2014.
19.
Barnett V. Comparative statistical inference. In: Barnett V, et al. editors. Wiley series in probability and statistics. 3rd ed. Chichester: Wiley; 1999.
20.
Buchholz AC, Rafii M, Pencharz PB. Is resting metabolic rate different between men and women? Br J Nutr. 2001;86(06):641–6.CrossRefPubMed
21.
Ferraro R, Lillioja S, Fontvieille A-M, Rising R, Bogardus C, Ravussin E. Lower sedentary metabolic rate in women compared with men. J Clin Invest. 1992;90(3):780.CrossRefPubMedPubMedCentral
22.
Rajender Reddy K, Modi MW, Pedder S. Use of peginterferon alfa-2a (40 kD) (Pegasys) for the treatment of hepatitis C. Adv Drug Deliv Rev. 2002;54(4):571–86.CrossRefPubMed
23.
Venkataramanan R, Swaminathan A, Prasad T, Jain A, Zuckerman S, Warty V, et al. Clinical pharmacokinetics of tacrolimus. Clin Pharmacokinet. 1995;29(6):404–30.CrossRefPubMed
24.
Legg B, Rowland M. Cyclosporin: measurement of fraction unbound in plasma. J Pharm Pharmacol. 1987;39(8):599–603.CrossRefPubMed
25.
Legg B, Gupta SK, Rowland M, Johnson RW, Solomon LR. Cyclosporin: pharmacokinetics and detailed studies of plasma and erythrocyte binding during intravenous and oral administration. Eur J Clin Pharmacol. 1988;34(5):451–60.CrossRefPubMed
26.
27.
Saleh MI, Obeidat AR, Anter HA, Khanfar AA. Eltrombopag dose predictors in thrombocytopenic subjects with hepatitis C virus infection. Clin Exp Pharmacol Physiol. 2015;42(10):1030–5.CrossRefPubMed
Metadata
Title
A Bayesian Approach for Population Pharmacokinetic Modeling of Pegylated Interferon α-2a in Hepatitis C Patients
Author
Mohammad I. Saleh
Publication date
01-11-2017
Publisher
Springer International Publishing
Published in
Clinical Pharmacokinetics / Issue 11/2017
Print ISSN: 0312-5963
Electronic ISSN: 1179-1926
DOI
https://doi.org/10.1007/s40262-017-0527-3

Other articles of this Issue 11/2017

Clinical Pharmacokinetics 11/2017 Go to the issue

Review Article

A Review of the Clinical Pharmacokinetics, Pharmacodynamics, and Immunogenicity of Vedolizumab

Original Research Article

Population Pharmacokinetic Analysis of Ixazomib, an Oral Proteasome Inhibitor, Including Data from the Phase III TOURMALINE-MM1 Study to Inform Labelling

Original Research Article

Development of a Pediatric Physiologically-Based Pharmacokinetic Model of Clindamycin Using Opportunistic Pharmacokinetic Data

Review Article

Levetiracetam Clinical Pharmacokinetic Monitoring in Pediatric Patients with Epilepsy

Original Research Article

No Dose Adjustment is Recommended for Digoxin, Warfarin, Atorvastatin or a Combination Oral Contraceptive When Coadministered with Dulaglutide

Systematic Review

Gestation-Specific Changes in the Anatomy and Physiology of Healthy Pregnant Women: An Extended Repository of Model Parameters for Physiologically Based Pharmacokinetic Modeling in Pregnancy