Pharmacokinetic and pharmacodynamic comparison of two "pegylated" interferon alpha-2 formulations in healthy male volunteers: a randomized, crossover, double-blind study
Open accessAbstract
BACKGROUND: Interferon (IFN) alpha conjugation to polyethylene glycol (PEG) results in a better pharmacokinetic profile and efficacy. The aim of this study was to compare the pharmacokinetic, pharmacodynamic and safety properties of a new, locally developed, 40-kDa PEG-IFN alpha-2b preparation with a reference, commercially available PEG-IFN alpha-2a in healthy male volunteers. METHODS: A randomized, crossover, double-blind study with a 3-weeks washout period, was done. A single 180 micrograms PEG-IFN alpha-2 dose was administered subcutaneously in both groups. Sixteen apparently healthy male subjects were included. Serum PEG-IFN concentration was measured during 336 hours by an enzyme immunoassay (EIA). Other clinical and laboratory variables were used as pharmacodynamic and safety criteria. RESULTS: The pharmacokinetic comparison by EIA yielded a high similitude between the formulations. In spite of a high subject variability, the parameters' mean were very close (in all cases p > 0.05): AUC: 53623 vs. 44311 pg.h/mL; Cmax: 333 vs. 271 pg/mL; Tmax: 54 vs. 55 h; half-life (t1/2): 72.4 vs. 64.8 h; terminal elimination rate (lambda): 0.011 vs. 0.014 h(-1); mean residence time (MRT): 135 vs. 123 h for reference and study preparations, respectively. There were no significant differences with respect to the pharmacodynamic variables either: serum neopterin and beta-2 microglobulin levels, stimulation of 2'5' oligoadenylate synthetase expression, and serum IFN antiviral activity. A strong Spearman's rank order correlation (p < 0.01) between the pharmacokinetic and pharmacodynamic concentration-time curves was observed. Both products caused similar leukocyte counts diminution and had similar safety profiles. The most frequent adverse reactions were leukopenia, fever, thrombocytopenia, transaminases increase and asthenia, mostly mild. CONCLUSIONS: Both formulations are fully comparable from the pharmacokinetic, pharmacodynamic, and safety profiles. Efficacy trials can be carried out to confirm clinical similarity.
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CXCR4 is a key regulator of HSC quiescence.
“In HSCs, we identified a downregulation of CXCR4 gene expression ( Fig. 2j, Supplementary Table 5) , a key regulator of HSC quiescence 45 , which may thus be involved in cell cycle entry of HSCs.”
From Type 1 interferon perturbates clonal competition by reshaping human blood development (2026) · cites this paper as [45]
The Discussion (page unavailable) describes interferon-induced pharmacodynamic markers, while Methods > Clinical and laboratory evaluations (page unavailable) describes measurement of 2',5' OAS expression. Searches for CXCR4, HSC quiescence, and hematopoietic stem-cell cell-cycle regulation found no passage in our copy addressing the attributed claim. (LLM, conf=0.77)
Experimental — accuracy not yet measuredIn HSCs, CXCR4 gene expression was downregulated upon IFNa treatment.
“In HSCs, we identified a downregulation of CXCR4 gene expression ( Fig. 2j, Supplementary Table 5) , a key regulator of HSC quiescence 45 , which may thus be involved in cell cycle entry of HSCs.”
From Type 1 interferon perturbates clonal competition by reshaping human blood development (2026) · cites this paper as [45]
Citation 45 is attached to the description of CXCR4 as a key regulator of HSC quiescence; the downregulation is presented as the citing authors’ own finding. The cited paper’s Methods and Discussion describe interferon-response measurements in healthy volunteers, but passages retrieved for CXCR4, HSCs, and quiescence do not address that regulatory role. (LLM, conf=0.76)
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Cites
Peginterferon Alfa-2a plus Ribavirin for Chronic Hepatitis C Virus Infection
Fried, M. W., Shiffman, M. L., Reddy, K. R., Smith, C. I., Marinos, G., Gonçales, F. L., Häussinger, D., Moisés Diago, M., Carosi, G., Dhumeaux, D., et al. (2002) · New England Journal of Medicine · doi:10.1056/nejmoa020047 · Cited by 6,386 · see citing works
Interferon-inducible antiviral effectors
Sadler, A. J., & Williams, B. R. G. (2008) · Nature Reviews Immunology · doi:10.1038/nri2314 · Cited by 2,160 · see citing works
Peginterferon Alfa-2a in Patients with Chronic Hepatitis C
Zeuzem, S., Feinman, S. V., Rasenack, J. W. F., Heathcote, E. J., Lai, M., Gane, E. J., O’Grady, J., Reichen, J., Moisés Diago, M., Lin, A., et al. (2000) · New England Journal of Medicine · doi:10.1056/nejm200012073432301 · Cited by 1,218 · see citing works
Peginterferon Alfa-2b or Alfa-2a with Ribavirin for Treatment of Hepatitis C Infection
McHutchison, J. G., Lawitz, E., Shiffman, M. L., Muir, A. J., Galler, G. W., McCone, J., Nyberg, L. M., Lee, W. M., Ghalib, R. H., Schiff, E. R., et al. (2009) · New England Journal of Medicine · doi:10.1056/nejmoa0808010 · Cited by 1,182 · see citing works
Neopterin as a Marker for Immune System Activation
Murr, C., Widner, B., Wirleitner, B., & Fuchs, D. (2002) · Current Drug Metabolism · doi:10.2174/1389200024605082 · Cited by 737 · see citing works
Pegylated interferon-α2b: Pharmacokinetics, pharmacodynamics, safety, and preliminary efficacy data
Glue, P. (2000) · Clinical Pharmacology & Therapeutics · doi:10.1067/mcp.2000.110973 · Cited by 504 · see citing works
MHC class I antigens, immune surveillance, and tumor immune escape
Garcia-Lora, A. M., Algarra, I., & Garrido, F. (2003) · Journal of Cellular Physiology · doi:10.1002/jcp.10290 · Cited by 502 · see citing works
Pharmacokinetic/Pharmacodynamic Studies in Drug Product Development
Meibohm, B., & Derendorf, H. (2002) · Journal of Pharmaceutical Sciences · doi:10.1002/jps.1167 · Cited by 157 · see citing works
Prophylactic action of oral fluconazole against fungal infection in neutropenic patients
Kanda, Y., Yamamoto, R., Chizuka, A., Hamaki, T., Suguro, M., Arai, C., Matsuyama, T., Takezako, N., Miwa, A., Kern, W., et al. (2000) · Cancer · doi:10.1002/1097-0142(20001001)89:7 · Cited by 151 · see citing works
Reigner, B. G., Williams, P. E. O., Patel, I. H., Steimer, J., Peck, C. C., & van Brummelen, P. (1997) · Clinical Pharmacokinetics · doi:10.2165/00003088-199733020-00005 · Cited by 121 · see citing works
Monkarsh, S. P., Ma, Y., Aglione, A., Bailon, P., Ciolek, D., Debarbieri, B., Graves, M. C., Hollfelder, K., Michel, H., Palleroni, A. V., et al. (1997) · Analytical Biochemistry · doi:10.1006/abio.1997.2128 · Cited by 114 · see citing works
Motzer, R. J., Rakhit, A. K., Ginsberg, M. S., Rittweger, K., Vuky, J., Yu, R., Fettner, S. H., & Hooftman, L. W. (2001) · Journal of Clinical Oncology · doi:10.1200/jco.2001.19.5.1312 · Cited by 101 · see citing works
PEGylated Interferon-α2b: A Branched 40K Polyethylene Glycol Derivative
Ramón, J., Saez, V. M., Báez, R., Aldana, R., & Hardy, E. (2005) · Pharmaceutical Research · doi:10.1007/s11095-005-5278-4 · Cited by 84 · see citing works
Effects of interferon-alpha (IFN-α) administration on leucocytes in healthy humans
Corssmit, E. P. M., Heijligenberg, R., Hack, C. E., Endert, E., Sauerwein, H. P., & Romijn, J. A. (1997) · Clinical & Experimental Immunology · doi:10.1111/j.1365-2249.1997.269-ce1161.x · Cited by 70 · see citing works
Individual Bioequivalence Revisited
Chen, M.-L., & Lesko, L. J. (2001) · Clinical Pharmacokinetics · doi:10.2165/00003088-200140100-00001 · Cited by 36 · see citing works
Bruno, R., Sacchi, P., Scagnolari, C., Torriani, F. J., Maiocchi, L., Patruno, S. F. A., Bellomi, F., Filice, G., & Antonelli, G. (2007) · Alimentary Pharmacology & Therapeutics · doi:10.1111/j.1365-2036.2007.03392.x · Cited by 36 · see citing works
Marcellini, M., Kondili, L. A., Comparcola, D., Spada, E., Sartorelli, M. R., Palumbo, M., & Rapicetta, M. (1997) · The Pediatric Infectious Disease Journal · doi:10.1097/00006454-199711000-00009 · Cited by 26 · see citing works
Wang, Y., Xu, W., Sun, X., Chen, Y., Liu, X., Tang, H., & Jiang, C. (2004) · Journal of Neuroimmunology · doi:10.1016/j.jneuroim.2004.07.013 · Cited by 18 · see citing works
PEGINTERFERON ALFA‐2A (40KD) (PEGASYS®) FOR THE TREATMENT OF PATIENTS WITH CHRONIC HEPATITIS C
Ferenci, P. (2003) · International Journal of Clinical Practice · doi:10.1111/j.1742-1241.2003.tb10568.x · Cited by 15 · see citing works
Pegylation of IFN- α and Antiviral Activity
Boulestin, A., Kamar, N., Sauné, K., Alric, L., Vinel, J., Rostaing, L. P. E., & Izopet, J. (2006) · Journal of Interferon & Cytokine Research · doi:10.1089/jir.2006.26.849 · Cited by 14 · see citing works
Bioequivalence of Two Recombinant Interferon ??-2b Liquid Formulations in Healthy Male Volunteers
García‐García, I., González-Delgado, C. A., Valenzuela‐Silva, C., Hernández‐Bernal, F., Ferrero-Bibilonia, J., Soto-Hernández, R., Cervantes‐Llanos, M., Ducong, J., Correa-Fernandez, A., Olivera-Ruano, L., et al. (2004) · Drugs in R&D · doi:10.2165/00126839-200405050-00003 · Cited by 9 · see citing works
Self-citationNapoli, N., Giannelli, G., Antonaci, A., & Antonaci, S. (2008) · Journal of Viral Hepatitis · doi:10.1111/j.1365-2893.2007.00944.x · Cited by 5 · see citing works
Flagged first, then by citations
Research works printed but not linked: 5
- Robins GW Scott LJ Keating GM PEG IFN-alpha-2a (40 kD): a review of its use in the management of patients with chronic hepatitis B Drugs 2005 65 809 825 10.2165/00003495-200565060-00010 15819595 · DOI
- Steinijans VW Hauschke D Update on the statistical analysis of bioequivalence studies Int J Clin Pharmacol Ther Toxicol 1990 28 105 110 2318545
- Steinijans VW Hauschke D A distribution-free procedure for the statistical analysis of bioequivalence studies Int J Clin Pharmacol Ther Toxicol 1990 28 72 78 2307548
- Xu ZX Hoffman J Patel I Jonbert P Single-dose safety/tolerability and pharmacokinetics/pharmacodynamics (PK/PD) following administration of ascending subcutaneous doses of pegylated-interferon (PEG-INF) and interferon α-2a (INF α-2a) to healthy subjects Hepatology 1998 28 702A 10.1002/hep.510280302 · DOI
- Gross G Ikenberg H Roussaki A Drees N Schopf E Systemic treatment of condylomata acuminata with recombinant interferon-alpha-2a: low-dose superior to the high-dose regimen Chemotherapy 1986 32 537 541 10.1159/000238464 3802956 · DOI
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Type 1 interferon perturbates clonal competition by reshaping human blood development
Lama, C., Isakov, D., Rosenberg, S., Quijada-Álamo, M., Saurty-Seerunghen, M. S., Moein, S., Nozais, M., Abera, T.-A., Sakaguchi, O., Totwani, M., et al. (2026) · Nature Genetics · doi:10.1038/s41588-026-02751-3 · Cited by 3 · see citing works
- Authors
- for the FarmaPEG Study Group, García-García, I., González-Delgado, C. A., Valenzuela-Silva, C. M., Díaz-Machado, A., Cruz-Díaz, M., Nodarse-Cuní, H., Pérez-Pérez, O., Bermúdez-Badell, C. H., Ferrero-Bibilonia, J., Páez-Meireles, R., Bello-Rivero, I., Castro-Odio, F. R., & López-Saura, P. A.
- Affiliations
- Centro de Ingeniería Genética y Biotecnología (CU)
- Venue
- BMC Pharmacology
- Published
- 2010-11-23
- Volume
- 10
- Issue
- 1
- Pages
- 15-15
- ISSN
- 1471-2210 (ISSN-L)
- PMC
- PMC3001701
- OpenAlex
- W2007828734
- Cited by
- 33
- References
- 22
- Citations by year
- 2026: 2 · 2025: 1 · 2022: 2 · 2021: 2 · 2020: 1 · 2019: 2 · 2018: 2 · 2017: 2 · 2016: 2 · 2015: 5 · 2014: 4 · 2013: 5 · 2012: 2
- FWCI
- 1.68
- Type
- journal article
- Language
- en
- Open access
- hybrid
- doi.org
- Licence
- Locations
- BMC Pharmacology (publishedVersion, cc-by)
- PubMed Central (publishedVersion, cc-by)
- PubMed (publishedVersion)
- Greater South Information System
- Topics
- Health Sciences › Medicine › Hepatology › Hepatitis C virus research
- Life Sciences › Immunology and Microbiology › Immunology › interferon and immune responses
- Life Sciences › Immunology and Microbiology › Immunology › Biosimilars and Bioanalytical Methods
- Keywords
- interferon alfa-2b, interferon alfa-2a, pharmacokinetics, pharmacodynamics, bioequivalence, neopterin, beta2-microglobulin, 2',5'-oligoadenylate synthetase, interferon antiviral activity, leukopenia, adverse drug reactions, antiviral therapy, healthy volunteers
- MeSH terms
- Interferon alpha-2, Adult, Antiviral Agents, beta 2-Microglobulin, Chemistry, Pharmaceutical, Double-Blind Method, Half-Life, Humans, Leukopenia, Male, Metabolic Clearance Rate, Microbial Sensitivity Tests, Polyethylene Glycols, Recombinant Proteins, RNA, Messenger, 2',5'-Oligoadenylate Synthetase, Biomarkers, Interferon-alpha, Cross-Over Studies, Neopterin, Young Adult
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