MONITORING AMPHOTERICIN B AND FLUCONAZOLE CONCENTRATIONS IN THE PLASMA AND CEREBROSPINAL FLUID OF PATIENTS WITH CRYPTOCOCCAL MENINGITIS
Autor(a) principal: | |
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Data de Publicação: | 2012 |
Outros Autores: | , , , |
Tipo de documento: | Artigo |
Idioma: | eng |
Título da fonte: | Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos) |
Texto Completo: | https://doi.org/10.25756/rpf.v4i4.61 |
Resumo: | Objectives: To determine whether amphotericin B (AmB) and fluconazole cross the blood-brain barrier in a similar manner in patients with HIV-associated cryptococcal meningitis based on the cerebrospinal fluid (CSF)/plasma drug ratio through a comparative study.Methods: This prospective, open-label clinical protocol included 21 male and female patients, 28-55 years of age. The patients were infected with HIV (CD4 50-200 cells/mL) and cryptococcal meningitis and were receiving AmB (1 mg/kg daily, infusion of four hours; 6-10 weeks) and fluconazole (400 mg 12 qh; until CSF was negative for fungal growth). The patients were informed in detail about all procedures to be performed in the hospital, including blood and CSF sample collection, if required. The study protocol was approved by the hospital’s ethical committee. Plasma samples were obtained by centrifugation at 2800 g for 30 min, and CSF samples were collected by the physician to relieve symptoms caused by intracranial hypertension. The drug concentrations of both antifungal agents were determined in the biological samples using HPLC.Results: The mean drug plasma: CSF concentrations were 2.30:0.3 μg/mL and 31.7:19.4 μg/mL for AmB and fluconazole, respectively. The CSF:plasma ratios were 0.20 (AmB) and 0.67 (fluconazole).Conclusions: Unlike fluconazole, the conventional AmB formulation did not reach the optimum CSF drug concentration. However, a high-dose regimen of fluconazole contributes to the outcome of HIV inpatients with severe cryptococcal meningites |
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MONITORING AMPHOTERICIN B AND FLUCONAZOLE CONCENTRATIONS IN THE PLASMA AND CEREBROSPINAL FLUID OF PATIENTS WITH CRYPTOCOCCAL MENINGITISMONITORING AMPHOTERICIN B AND FLUCONAZOLE CONCENTRATIONS IN THE PLASMA AND CEREBROSPINAL FLUID OF PATIENTS WITH CRYPTOCOCCAL MENINGITISObjectives: To determine whether amphotericin B (AmB) and fluconazole cross the blood-brain barrier in a similar manner in patients with HIV-associated cryptococcal meningitis based on the cerebrospinal fluid (CSF)/plasma drug ratio through a comparative study.Methods: This prospective, open-label clinical protocol included 21 male and female patients, 28-55 years of age. The patients were infected with HIV (CD4 50-200 cells/mL) and cryptococcal meningitis and were receiving AmB (1 mg/kg daily, infusion of four hours; 6-10 weeks) and fluconazole (400 mg 12 qh; until CSF was negative for fungal growth). The patients were informed in detail about all procedures to be performed in the hospital, including blood and CSF sample collection, if required. The study protocol was approved by the hospital’s ethical committee. Plasma samples were obtained by centrifugation at 2800 g for 30 min, and CSF samples were collected by the physician to relieve symptoms caused by intracranial hypertension. The drug concentrations of both antifungal agents were determined in the biological samples using HPLC.Results: The mean drug plasma: CSF concentrations were 2.30:0.3 μg/mL and 31.7:19.4 μg/mL for AmB and fluconazole, respectively. The CSF:plasma ratios were 0.20 (AmB) and 0.67 (fluconazole).Conclusions: Unlike fluconazole, the conventional AmB formulation did not reach the optimum CSF drug concentration. However, a high-dose regimen of fluconazole contributes to the outcome of HIV inpatients with severe cryptococcal meningitesObjetivos: Através de estudo comparativo em pacientes HIV positivo com meningite criptocócica, investigar se a anfotericina B (AmB) e o fluconazol atravessam a barreira hematoencefálica de forma semelhante, com base na razão entre a concentração dos fármacos no líquor e no plasma.Métodos: Vinte e um pacientes, de ambos os sexos, com idades entre os 28 e os 55 anos, foram incluídos neste protocolo clínico aberto e prospetivo; todos apresentaram meningite criptocócica e HIV positivo (CD4 50-200) e foram submetidos ao tratamento com AmB (1 mg/kg, uma vez ao dia, infusão de quatro horas; por seis a dez semanas) e fluconazol (400 mg, 12/12 hs.; até crescimento fúngico negativo no líquor). Todos os pacientes foram informados em detalhe sobre os procedimentos a realizar no hospital, incluindo a coleta de sangue e líquor, se necessário. O protocolo foi aprovado pelo Comitê de Ética do hospital. O plasma foi obtido através de centrifugação do sangue a 2800 g por 30 min.; para o alívio dos sintomas decorrentes da hipertensão intracraniana, as amostras do líquor foram coletadas pelo médico responsável. A concentração dos antifúngicos foi determinada através de CLAE.Resultados: As concentrações médias da AmB e do fluconazol no plasma (P) e no líquor (L) foram, respetivamente, 2,30:0,3 μg/mL e 31,7:19,4 μg/mL (P:F). A travessia através da barreira hematoencefálica foi estimada pela razão líquor/plasma e os resultados obtidos no estudo foram 0,20 (AmB) versus 0,67 (fluconazol). Conclusões: Comparado ao fluconazol, a formulação convencional de AmB não atingiu concentrações adequadas no líquor; desta forma, o fluconazol em regime de alta dose contribuiu para o desfecho dos pacientes com HIV e meningite criptocócica tratados com esses dois antifúngicos.Formifarma2012-12-28info:eu-repo/semantics/publishedVersioninfo:eu-repo/semantics/articleapplication/pdfhttps://doi.org/10.25756/rpf.v4i4.61https://doi.org/10.25756/rpf.v4i4.61Revista Portuguesa de Farmacoterapia / Portuguese Journal of Pharmacotherapy; Vol 4 No 4 (2012): Outubro; 15-18Revista Portuguesa de Farmacoterapia; v. 4 n. 4 (2012): Outubro; 15-182183-73411647-354Xreponame:Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos)instname:Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informaçãoinstacron:RCAAPenghttp://revista.farmacoterapia.pt/index.php/rpf/article/view/61http://revista.farmacoterapia.pt/index.php/rpf/article/view/61/49Direitos de Autor (c) 2017 Revista Portuguesa de Farmacoterapiahttp://creativecommons.org/licenses/by-nc-nd/4.0info:eu-repo/semantics/openAccessSantos, Sílvia Regina Cavani JorgeSilva Martins Pappalardo, Mara CristinaPerez, Grazziela SamanthaSanches-Giraud, CristinaSouza Carvalho Melhem, Márcia2023-09-01T04:33:11Zoai:ojs.farmacoterapia.pt:article/61Portal AgregadorONGhttps://www.rcaap.pt/oai/openaireopendoar:71602024-03-19T15:11:32.040058Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos) - Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informaçãofalse |
dc.title.none.fl_str_mv |
MONITORING AMPHOTERICIN B AND FLUCONAZOLE CONCENTRATIONS IN THE PLASMA AND CEREBROSPINAL FLUID OF PATIENTS WITH CRYPTOCOCCAL MENINGITIS MONITORING AMPHOTERICIN B AND FLUCONAZOLE CONCENTRATIONS IN THE PLASMA AND CEREBROSPINAL FLUID OF PATIENTS WITH CRYPTOCOCCAL MENINGITIS |
title |
MONITORING AMPHOTERICIN B AND FLUCONAZOLE CONCENTRATIONS IN THE PLASMA AND CEREBROSPINAL FLUID OF PATIENTS WITH CRYPTOCOCCAL MENINGITIS |
spellingShingle |
MONITORING AMPHOTERICIN B AND FLUCONAZOLE CONCENTRATIONS IN THE PLASMA AND CEREBROSPINAL FLUID OF PATIENTS WITH CRYPTOCOCCAL MENINGITIS Santos, Sílvia Regina Cavani Jorge |
title_short |
MONITORING AMPHOTERICIN B AND FLUCONAZOLE CONCENTRATIONS IN THE PLASMA AND CEREBROSPINAL FLUID OF PATIENTS WITH CRYPTOCOCCAL MENINGITIS |
title_full |
MONITORING AMPHOTERICIN B AND FLUCONAZOLE CONCENTRATIONS IN THE PLASMA AND CEREBROSPINAL FLUID OF PATIENTS WITH CRYPTOCOCCAL MENINGITIS |
title_fullStr |
MONITORING AMPHOTERICIN B AND FLUCONAZOLE CONCENTRATIONS IN THE PLASMA AND CEREBROSPINAL FLUID OF PATIENTS WITH CRYPTOCOCCAL MENINGITIS |
title_full_unstemmed |
MONITORING AMPHOTERICIN B AND FLUCONAZOLE CONCENTRATIONS IN THE PLASMA AND CEREBROSPINAL FLUID OF PATIENTS WITH CRYPTOCOCCAL MENINGITIS |
title_sort |
MONITORING AMPHOTERICIN B AND FLUCONAZOLE CONCENTRATIONS IN THE PLASMA AND CEREBROSPINAL FLUID OF PATIENTS WITH CRYPTOCOCCAL MENINGITIS |
author |
Santos, Sílvia Regina Cavani Jorge |
author_facet |
Santos, Sílvia Regina Cavani Jorge Silva Martins Pappalardo, Mara Cristina Perez, Grazziela Samantha Sanches-Giraud, Cristina Souza Carvalho Melhem, Márcia |
author_role |
author |
author2 |
Silva Martins Pappalardo, Mara Cristina Perez, Grazziela Samantha Sanches-Giraud, Cristina Souza Carvalho Melhem, Márcia |
author2_role |
author author author author |
dc.contributor.author.fl_str_mv |
Santos, Sílvia Regina Cavani Jorge Silva Martins Pappalardo, Mara Cristina Perez, Grazziela Samantha Sanches-Giraud, Cristina Souza Carvalho Melhem, Márcia |
description |
Objectives: To determine whether amphotericin B (AmB) and fluconazole cross the blood-brain barrier in a similar manner in patients with HIV-associated cryptococcal meningitis based on the cerebrospinal fluid (CSF)/plasma drug ratio through a comparative study.Methods: This prospective, open-label clinical protocol included 21 male and female patients, 28-55 years of age. The patients were infected with HIV (CD4 50-200 cells/mL) and cryptococcal meningitis and were receiving AmB (1 mg/kg daily, infusion of four hours; 6-10 weeks) and fluconazole (400 mg 12 qh; until CSF was negative for fungal growth). The patients were informed in detail about all procedures to be performed in the hospital, including blood and CSF sample collection, if required. The study protocol was approved by the hospital’s ethical committee. Plasma samples were obtained by centrifugation at 2800 g for 30 min, and CSF samples were collected by the physician to relieve symptoms caused by intracranial hypertension. The drug concentrations of both antifungal agents were determined in the biological samples using HPLC.Results: The mean drug plasma: CSF concentrations were 2.30:0.3 μg/mL and 31.7:19.4 μg/mL for AmB and fluconazole, respectively. The CSF:plasma ratios were 0.20 (AmB) and 0.67 (fluconazole).Conclusions: Unlike fluconazole, the conventional AmB formulation did not reach the optimum CSF drug concentration. However, a high-dose regimen of fluconazole contributes to the outcome of HIV inpatients with severe cryptococcal meningites |
publishDate |
2012 |
dc.date.none.fl_str_mv |
2012-12-28 |
dc.type.status.fl_str_mv |
info:eu-repo/semantics/publishedVersion |
dc.type.driver.fl_str_mv |
info:eu-repo/semantics/article |
format |
article |
status_str |
publishedVersion |
dc.identifier.uri.fl_str_mv |
https://doi.org/10.25756/rpf.v4i4.61 https://doi.org/10.25756/rpf.v4i4.61 |
url |
https://doi.org/10.25756/rpf.v4i4.61 |
dc.language.iso.fl_str_mv |
eng |
language |
eng |
dc.relation.none.fl_str_mv |
http://revista.farmacoterapia.pt/index.php/rpf/article/view/61 http://revista.farmacoterapia.pt/index.php/rpf/article/view/61/49 |
dc.rights.driver.fl_str_mv |
Direitos de Autor (c) 2017 Revista Portuguesa de Farmacoterapia http://creativecommons.org/licenses/by-nc-nd/4.0 info:eu-repo/semantics/openAccess |
rights_invalid_str_mv |
Direitos de Autor (c) 2017 Revista Portuguesa de Farmacoterapia http://creativecommons.org/licenses/by-nc-nd/4.0 |
eu_rights_str_mv |
openAccess |
dc.format.none.fl_str_mv |
application/pdf |
dc.publisher.none.fl_str_mv |
Formifarma |
publisher.none.fl_str_mv |
Formifarma |
dc.source.none.fl_str_mv |
Revista Portuguesa de Farmacoterapia / Portuguese Journal of Pharmacotherapy; Vol 4 No 4 (2012): Outubro; 15-18 Revista Portuguesa de Farmacoterapia; v. 4 n. 4 (2012): Outubro; 15-18 2183-7341 1647-354X reponame:Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos) instname:Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informação instacron:RCAAP |
instname_str |
Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informação |
instacron_str |
RCAAP |
institution |
RCAAP |
reponame_str |
Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos) |
collection |
Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos) |
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Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos) - Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informação |
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1799129986078081024 |