Pharmacokinetics comparison of two pegylated interferon alfa formulations in healthy volunteers
Autor(a) principal: | |
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Data de Publicação: | 2018 |
Outros Autores: | , , , , , , , , , , |
Tipo de documento: | Artigo |
Idioma: | eng |
Título da fonte: | Repositório Institucional da UFRGS |
Texto Completo: | http://hdl.handle.net/10183/196689 |
Resumo: | Background: Several countries have used pegylation technology to improve the pharmacokinetic properties of essential drugs. Recently, a novel interferon alfa-2b protein conjugated to four-branched 12 kDa polyethylene glycol molecules was developed jointly between Cuba and Brazil. The aim of this study was to compare the pharmacokinetic properties of BIP48 (pegylated interferon alfa-2b from Bio-Manguinhos/Fiocruz, Brazil) to those of PEGASYS® (commercially available pegylated interferon alfa-2a from Roche Pharmaceutical). Methods: This phase I, single-centre, randomized, double-blind crossover trial enrolled 31 healthy male volunteers aged 19 to 35 who were allocated to two stages, either side of a 5-week wash-out period, with each arm lasting 14 consecutive days after subcutaneous administration of 180 μg of one formulation or the other (study or comparator). The main outcome variable was serum pegylated interferon concentrations in 15 samples collected during the course of the study and tested using an enzyme immunoassay. Results: There were no differences between formulations in terms of magnitude or absorption parameters. Analysis of time parameters revealed that BIP48 remained in the body significantly longer than PEGASYS® (Tmax: 73 vs. 54 h [p = 0.0010]; MRT: 133 vs. 115 h [p = 0.0324]; ke: 0.011 vs. 0.013 h(−1) [p = 0.0153]; t1/2: 192 vs. 108 h [p = 0.0218]). Conclusion: BIP48 showed the expected pharmacokinetic profile for a pegylated product with a branched molecular structure. Compared to PEGASYS®, the magnitude absorption was similar, but time parameters were consistent with slower elimination. Further studies should be conducted to evaluate the clinical implications of these findings. A phase II-III repeated-dose clinical trial is ongoing to study these findings in patients with chronic hepatitis C virus infection. |
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Costa, Marisa Boff daPicon, Paulo DornellesSander, Guilherme BeckerNodarse Cuni, HugoValenzuela Silva, Carmen MPáez Meireles, RolandoGóes, Ana Carolina Magalhães AndradeBatoreu, Nadia MariaMaia, Maria de Lourdes de SousaAlbuquerque, Elizabeth MacielMatos, Denise Cristina de SouzaLópez Saura, Pedro Antonio2019-07-09T02:38:41Z20182050-6511http://hdl.handle.net/10183/196689001096129Background: Several countries have used pegylation technology to improve the pharmacokinetic properties of essential drugs. Recently, a novel interferon alfa-2b protein conjugated to four-branched 12 kDa polyethylene glycol molecules was developed jointly between Cuba and Brazil. The aim of this study was to compare the pharmacokinetic properties of BIP48 (pegylated interferon alfa-2b from Bio-Manguinhos/Fiocruz, Brazil) to those of PEGASYS® (commercially available pegylated interferon alfa-2a from Roche Pharmaceutical). Methods: This phase I, single-centre, randomized, double-blind crossover trial enrolled 31 healthy male volunteers aged 19 to 35 who were allocated to two stages, either side of a 5-week wash-out period, with each arm lasting 14 consecutive days after subcutaneous administration of 180 μg of one formulation or the other (study or comparator). The main outcome variable was serum pegylated interferon concentrations in 15 samples collected during the course of the study and tested using an enzyme immunoassay. Results: There were no differences between formulations in terms of magnitude or absorption parameters. Analysis of time parameters revealed that BIP48 remained in the body significantly longer than PEGASYS® (Tmax: 73 vs. 54 h [p = 0.0010]; MRT: 133 vs. 115 h [p = 0.0324]; ke: 0.011 vs. 0.013 h(−1) [p = 0.0153]; t1/2: 192 vs. 108 h [p = 0.0218]). Conclusion: BIP48 showed the expected pharmacokinetic profile for a pegylated product with a branched molecular structure. Compared to PEGASYS®, the magnitude absorption was similar, but time parameters were consistent with slower elimination. Further studies should be conducted to evaluate the clinical implications of these findings. A phase II-III repeated-dose clinical trial is ongoing to study these findings in patients with chronic hepatitis C virus infection.application/pdfengBMC pharmacology and toxicology. London. Vol. 19, no. 1 (2018), 8 p.FarmacocinéticaInterferon alfaAntiviraisPharmacokineticsPegylated interferon-alfaPhase IPharmacokinetics comparison of two pegylated interferon alfa formulations in healthy volunteersEstrangeiroinfo:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersioninfo:eu-repo/semantics/openAccessreponame:Repositório Institucional da UFRGSinstname:Universidade Federal do Rio Grande do Sul (UFRGS)instacron:UFRGSTEXT001096129.pdf.txt001096129.pdf.txtExtracted Texttext/plain38667http://www.lume.ufrgs.br/bitstream/10183/196689/2/001096129.pdf.txt38b45bef1b81abda1781e84b4e874223MD52ORIGINAL001096129.pdfTexto completo (inglês)application/pdf602092http://www.lume.ufrgs.br/bitstream/10183/196689/1/001096129.pdffffa5d9a393984922af123c83a788c9aMD5110183/1966892019-07-10 02:34:46.368303oai:www.lume.ufrgs.br:10183/196689Repositório de PublicaçõesPUBhttps://lume.ufrgs.br/oai/requestopendoar:2019-07-10T05:34:46Repositório Institucional da UFRGS - Universidade Federal do Rio Grande do Sul (UFRGS)false |
dc.title.pt_BR.fl_str_mv |
Pharmacokinetics comparison of two pegylated interferon alfa formulations in healthy volunteers |
title |
Pharmacokinetics comparison of two pegylated interferon alfa formulations in healthy volunteers |
spellingShingle |
Pharmacokinetics comparison of two pegylated interferon alfa formulations in healthy volunteers Costa, Marisa Boff da Farmacocinética Interferon alfa Antivirais Pharmacokinetics Pegylated interferon-alfa Phase I |
title_short |
Pharmacokinetics comparison of two pegylated interferon alfa formulations in healthy volunteers |
title_full |
Pharmacokinetics comparison of two pegylated interferon alfa formulations in healthy volunteers |
title_fullStr |
Pharmacokinetics comparison of two pegylated interferon alfa formulations in healthy volunteers |
title_full_unstemmed |
Pharmacokinetics comparison of two pegylated interferon alfa formulations in healthy volunteers |
title_sort |
Pharmacokinetics comparison of two pegylated interferon alfa formulations in healthy volunteers |
author |
Costa, Marisa Boff da |
author_facet |
Costa, Marisa Boff da Picon, Paulo Dornelles Sander, Guilherme Becker Nodarse Cuni, Hugo Valenzuela Silva, Carmen M Páez Meireles, Rolando Góes, Ana Carolina Magalhães Andrade Batoreu, Nadia Maria Maia, Maria de Lourdes de Sousa Albuquerque, Elizabeth Maciel Matos, Denise Cristina de Souza López Saura, Pedro Antonio |
author_role |
author |
author2 |
Picon, Paulo Dornelles Sander, Guilherme Becker Nodarse Cuni, Hugo Valenzuela Silva, Carmen M Páez Meireles, Rolando Góes, Ana Carolina Magalhães Andrade Batoreu, Nadia Maria Maia, Maria de Lourdes de Sousa Albuquerque, Elizabeth Maciel Matos, Denise Cristina de Souza López Saura, Pedro Antonio |
author2_role |
author author author author author author author author author author author |
dc.contributor.author.fl_str_mv |
Costa, Marisa Boff da Picon, Paulo Dornelles Sander, Guilherme Becker Nodarse Cuni, Hugo Valenzuela Silva, Carmen M Páez Meireles, Rolando Góes, Ana Carolina Magalhães Andrade Batoreu, Nadia Maria Maia, Maria de Lourdes de Sousa Albuquerque, Elizabeth Maciel Matos, Denise Cristina de Souza López Saura, Pedro Antonio |
dc.subject.por.fl_str_mv |
Farmacocinética Interferon alfa Antivirais |
topic |
Farmacocinética Interferon alfa Antivirais Pharmacokinetics Pegylated interferon-alfa Phase I |
dc.subject.eng.fl_str_mv |
Pharmacokinetics Pegylated interferon-alfa Phase I |
description |
Background: Several countries have used pegylation technology to improve the pharmacokinetic properties of essential drugs. Recently, a novel interferon alfa-2b protein conjugated to four-branched 12 kDa polyethylene glycol molecules was developed jointly between Cuba and Brazil. The aim of this study was to compare the pharmacokinetic properties of BIP48 (pegylated interferon alfa-2b from Bio-Manguinhos/Fiocruz, Brazil) to those of PEGASYS® (commercially available pegylated interferon alfa-2a from Roche Pharmaceutical). Methods: This phase I, single-centre, randomized, double-blind crossover trial enrolled 31 healthy male volunteers aged 19 to 35 who were allocated to two stages, either side of a 5-week wash-out period, with each arm lasting 14 consecutive days after subcutaneous administration of 180 μg of one formulation or the other (study or comparator). The main outcome variable was serum pegylated interferon concentrations in 15 samples collected during the course of the study and tested using an enzyme immunoassay. Results: There were no differences between formulations in terms of magnitude or absorption parameters. Analysis of time parameters revealed that BIP48 remained in the body significantly longer than PEGASYS® (Tmax: 73 vs. 54 h [p = 0.0010]; MRT: 133 vs. 115 h [p = 0.0324]; ke: 0.011 vs. 0.013 h(−1) [p = 0.0153]; t1/2: 192 vs. 108 h [p = 0.0218]). Conclusion: BIP48 showed the expected pharmacokinetic profile for a pegylated product with a branched molecular structure. Compared to PEGASYS®, the magnitude absorption was similar, but time parameters were consistent with slower elimination. Further studies should be conducted to evaluate the clinical implications of these findings. A phase II-III repeated-dose clinical trial is ongoing to study these findings in patients with chronic hepatitis C virus infection. |
publishDate |
2018 |
dc.date.issued.fl_str_mv |
2018 |
dc.date.accessioned.fl_str_mv |
2019-07-09T02:38:41Z |
dc.type.driver.fl_str_mv |
Estrangeiro info:eu-repo/semantics/article |
dc.type.status.fl_str_mv |
info:eu-repo/semantics/publishedVersion |
format |
article |
status_str |
publishedVersion |
dc.identifier.uri.fl_str_mv |
http://hdl.handle.net/10183/196689 |
dc.identifier.issn.pt_BR.fl_str_mv |
2050-6511 |
dc.identifier.nrb.pt_BR.fl_str_mv |
001096129 |
identifier_str_mv |
2050-6511 001096129 |
url |
http://hdl.handle.net/10183/196689 |
dc.language.iso.fl_str_mv |
eng |
language |
eng |
dc.relation.ispartof.pt_BR.fl_str_mv |
BMC pharmacology and toxicology. London. Vol. 19, no. 1 (2018), 8 p. |
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openAccess |
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