Randomized clinical trial comparing the pharmacokinetics of standard- and increased-dosage lopinavir-ritonavir coformulation tablets in hiv-positive pregnant women
| Autor(a) principal: | |
|---|---|
| Data de Publicação: | 2014 |
| Outros Autores: | , , , , , , , , , , |
| Tipo de documento: | Artigo |
| Idioma: | eng |
| Título da fonte: | Repositório Institucional da FIOCRUZ (ARCA) |
| Texto Completo: | https://www.arca.fiocruz.br/handle/icict/11352 |
Resumo: | This trial was supported by a grant from the Brazilian National AIDS Program-Ministry of Health. We thank Abbott Laboratories who donated lopinavir, ritonavir, and internal standard for the pharmacokinetics assay. |
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Oliveira, Marilia SantiniEstrela, Rita de Cássia EliasVeloso, Valdiléa G.Cattani, Vitória BergYanavich, CarolynVelasque, LucianeTorres, Thiago SilvaMarins, Luana Monteiro SpindolaPilotto, José HenriqueJoão, Esaú CustódioGonçalves, José Carlos SaraivaGrinsztejn, Beatriz2015-07-14T13:03:02Z2015-07-14T13:03:02Z2014OLIVEIRA, Marilia Santini et al. Randomized clinical trial comparing the pharmacokinetics of standard- and increased-dosage lopinavir-ritonavir coformulation tablets in hiv-positive pregnant women. Antimicrobial Agents and Chemotherapy, v. 58, n. 5, p. 2884-2893, May 2014.0066-4804https://www.arca.fiocruz.br/handle/icict/1135210.1128/AAC.02599-131098-6596This trial was supported by a grant from the Brazilian National AIDS Program-Ministry of Health. We thank Abbott Laboratories who donated lopinavir, ritonavir, and internal standard for the pharmacokinetics assay.Fundação Oswaldo Cruz. Instituto Nacional de Infectologia Evandro Chagas. Laboratório de Pesquisa Clínica em DST/AIDS. Rio de Janeiro, RJ, Brasil.Universidade Federal do Rio de Janeiro. Faculdade de Farmácia. Centro de Ciências da Saúde. Laboratório de Farmacometria LabFarma. Rio de Janeiro, RJ, Brasil.Fundação Oswaldo Cruz. Instituto Nacional de Infectologia Evandro Chagas. Laboratório de Pesquisa Clínica em DST/AIDS. Rio de Janeiro, RJ, Brasil.Fundação Oswaldo Cruz. Instituto Nacional de Infectologia Evandro Chagas. Laboratório de Pesquisa Clínica em DST/AIDS. Rio de Janeiro, RJ, Brasil.Children’s Hospital of Los Angeles. Division of Infectious Diseases. Los Angeles, CA, USA.Universidade Federal do Estado do Rio de Janeiro. Departamento de Matemática. Rio de Janeiro, RJ, Brasil.Fundação Oswaldo Cruz. Instituto Nacional de Infectologia Evandro Chagas. Laboratório de Pesquisa Clínica em DST/AIDS. Rio de Janeiro, RJ, Brasil.Fundação Oswaldo Cruz. Instituto Nacional de Infectologia Evandro Chagas. Laboratório de Pesquisa Clínica em DST/AIDS. Rio de Janeiro, RJ, Brasil.Fundação Oswaldo Cruz. Instituto Oswaldo Cruz. Laboratório de AIDS e Imunologia Molecular. Rio de Janeiro, RJ, Brasil / Hospital Geral de Nova Iguaçu. Nova Iguaçu, RJ, Brasil.Hospital Federal dos Servidores do Estado. Serviço de Doenças Infecciosas e Parasitárias. Rio de Janeiro, RJ, Brasil.Universidade Federal do Rio de Janeiro. Faculdade de Farmácia. Centro de Ciências da Saúde. Laboratório de Farmacometria LabFarma. Rio de Janeiro, RJ, Brasil.Fundação Oswaldo Cruz. Instituto Nacional de Infectologia Evandro Chagas. Laboratório de Pesquisa Clínica em DST/AIDS. Rio de Janeiro, RJ, Brasil.A lopinavir-ritonavir (LPV/r)-based regimen is recommended during pregnancy to reduce the risk of HIV mother-to-child transmission, but the appropriate dose is controversial. We compared the pharmacokinetics of standard and increased LPV/r doses during pregnancy. This randomized, open-label prospective study enrolled 60 pregnant women between gestational weeks 14 and 30. The participants received either the standard dose (400/100 mg twice a day [BID]) or increased dose (600/150 mg BID) of LPV/r tablets during pregnancy and the standard dose for 6 weeks after childbirth. Pharmacokinetics analysis was performed using a high-performance liquid chromatography-tandem mass spectrometry method. Adherent participants who received the standard dose presented minimum LPV concentrations of 4.4, 4.3, and 6.1 g/ml in the second and third trimesters and postpartum, respectively. The increased-dose group exhibited values of 7.9, 6.9, and 9.2 g/ml at the same three time points. Although LPV exposure was significantly higher in the increased-dose group, the standard dose produced therapeutic levels of LPV against wild-type virus in all adherent participants, except one patient in the third trimester; 50%, 37.5%, and 25%, and 0%, 15%, and 0% of the participants in the standard- and increased-dose groups failed to achieve therapeutic levels against resistant viruses during the second and third trimesters and after childbirth, respectively. After 12 weeks of treatment and after childbirth, all adherent participants achieved undetectable HIV viral loads, and their babies (49/54) were uninfected. No serious drug-related adverse events were observed. We conclude that the standard dose is appropriate for use during pregnancy and that an increased dose may be necessary for women harboring resistant HIV. (This study has been registered at ClinicalTrials.gov under registration no. NCT00605098).engAmerican Society for MicrobiologyRandomized clinical trial comparing the pharmacokinetics of standard- and increased-dosage lopinavir-ritonavir coformulation tablets in hiv-positive pregnant womeninfo:eu-repo/semantics/publishedVersioninfo:eu-repo/semantics/articlePharmacokineticsHIVPregnant WomenStatistical AnalysisFarmacocinéticaHIVGestantesAnálise Estatísticainfo:eu-repo/semantics/openAccessreponame:Repositório Institucional da FIOCRUZ (ARCA)instname:Fundação Oswaldo Cruz (FIOCRUZ)instacron:FIOCRUZLICENSElicense.txtlicense.txttext/plain; charset=utf-82354https://www.arca.fiocruz.br/bitstream/icict/11352/1/license.txt8b4c200b4e10021c5683c6ccaba07169MD51ORIGINALRandomized Clinical Trial Comparing the Pharmacokinetics of.pdfRandomized Clinical Trial Comparing the Pharmacokinetics of.pdfapplication/pdf1212321https://www.arca.fiocruz.br/bitstream/icict/11352/2/Randomized%20Clinical%20Trial%20Comparing%20the%20Pharmacokinetics%20of.pdf398a4bff754038300514a5be3c821c80MD52TEXTRandomized Clinical Trial Comparing the Pharmacokinetics of.pdf.txtRandomized Clinical Trial Comparing the Pharmacokinetics of.pdf.txtExtracted texttext/plain56103https://www.arca.fiocruz.br/bitstream/icict/11352/3/Randomized%20Clinical%20Trial%20Comparing%20the%20Pharmacokinetics%20of.pdf.txt1b4296c98e0e606b88c3332d5a3c592dMD53icict/113522023-09-04 11:30:14.658oai:www.arca.fiocruz.br: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Repositório InstitucionalPUBhttps://www.arca.fiocruz.br/oai/requestrepositorio.arca@fiocruz.bropendoar:21352023-09-04T14:30:14Repositório Institucional da FIOCRUZ (ARCA) - Fundação Oswaldo Cruz (FIOCRUZ)false |
| dc.title.pt_BR.fl_str_mv |
Randomized clinical trial comparing the pharmacokinetics of standard- and increased-dosage lopinavir-ritonavir coformulation tablets in hiv-positive pregnant women |
| title |
Randomized clinical trial comparing the pharmacokinetics of standard- and increased-dosage lopinavir-ritonavir coformulation tablets in hiv-positive pregnant women |
| spellingShingle |
Randomized clinical trial comparing the pharmacokinetics of standard- and increased-dosage lopinavir-ritonavir coformulation tablets in hiv-positive pregnant women Oliveira, Marilia Santini Pharmacokinetics HIV Pregnant Women Statistical Analysis Farmacocinética HIV Gestantes Análise Estatística |
| title_short |
Randomized clinical trial comparing the pharmacokinetics of standard- and increased-dosage lopinavir-ritonavir coformulation tablets in hiv-positive pregnant women |
| title_full |
Randomized clinical trial comparing the pharmacokinetics of standard- and increased-dosage lopinavir-ritonavir coformulation tablets in hiv-positive pregnant women |
| title_fullStr |
Randomized clinical trial comparing the pharmacokinetics of standard- and increased-dosage lopinavir-ritonavir coformulation tablets in hiv-positive pregnant women |
| title_full_unstemmed |
Randomized clinical trial comparing the pharmacokinetics of standard- and increased-dosage lopinavir-ritonavir coformulation tablets in hiv-positive pregnant women |
| title_sort |
Randomized clinical trial comparing the pharmacokinetics of standard- and increased-dosage lopinavir-ritonavir coformulation tablets in hiv-positive pregnant women |
| author |
Oliveira, Marilia Santini |
| author_facet |
Oliveira, Marilia Santini Estrela, Rita de Cássia Elias Veloso, Valdiléa G. Cattani, Vitória Berg Yanavich, Carolyn Velasque, Luciane Torres, Thiago Silva Marins, Luana Monteiro Spindola Pilotto, José Henrique João, Esaú Custódio Gonçalves, José Carlos Saraiva Grinsztejn, Beatriz |
| author_role |
author |
| author2 |
Estrela, Rita de Cássia Elias Veloso, Valdiléa G. Cattani, Vitória Berg Yanavich, Carolyn Velasque, Luciane Torres, Thiago Silva Marins, Luana Monteiro Spindola Pilotto, José Henrique João, Esaú Custódio Gonçalves, José Carlos Saraiva Grinsztejn, Beatriz |
| author2_role |
author author author author author author author author author author author |
| dc.contributor.author.fl_str_mv |
Oliveira, Marilia Santini Estrela, Rita de Cássia Elias Veloso, Valdiléa G. Cattani, Vitória Berg Yanavich, Carolyn Velasque, Luciane Torres, Thiago Silva Marins, Luana Monteiro Spindola Pilotto, José Henrique João, Esaú Custódio Gonçalves, José Carlos Saraiva Grinsztejn, Beatriz |
| dc.subject.en.pt_BR.fl_str_mv |
Pharmacokinetics HIV Pregnant Women Statistical Analysis |
| topic |
Pharmacokinetics HIV Pregnant Women Statistical Analysis Farmacocinética HIV Gestantes Análise Estatística |
| dc.subject.decs.pt_BR.fl_str_mv |
Farmacocinética HIV Gestantes Análise Estatística |
| description |
This trial was supported by a grant from the Brazilian National AIDS Program-Ministry of Health. We thank Abbott Laboratories who donated lopinavir, ritonavir, and internal standard for the pharmacokinetics assay. |
| publishDate |
2014 |
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2014 |
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2015-07-14T13:03:02Z |
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2015-07-14T13:03:02Z |
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info:eu-repo/semantics/publishedVersion |
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info:eu-repo/semantics/article |
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| dc.identifier.citation.fl_str_mv |
OLIVEIRA, Marilia Santini et al. Randomized clinical trial comparing the pharmacokinetics of standard- and increased-dosage lopinavir-ritonavir coformulation tablets in hiv-positive pregnant women. Antimicrobial Agents and Chemotherapy, v. 58, n. 5, p. 2884-2893, May 2014. |
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https://www.arca.fiocruz.br/handle/icict/11352 |
| dc.identifier.issn.none.fl_str_mv |
0066-4804 |
| dc.identifier.doi.none.fl_str_mv |
10.1128/AAC.02599-13 |
| dc.identifier.eissn.none.fl_str_mv |
1098-6596 |
| identifier_str_mv |
OLIVEIRA, Marilia Santini et al. Randomized clinical trial comparing the pharmacokinetics of standard- and increased-dosage lopinavir-ritonavir coformulation tablets in hiv-positive pregnant women. Antimicrobial Agents and Chemotherapy, v. 58, n. 5, p. 2884-2893, May 2014. 0066-4804 10.1128/AAC.02599-13 1098-6596 |
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https://www.arca.fiocruz.br/handle/icict/11352 |
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American Society for Microbiology |
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American Society for Microbiology |
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