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Randomised Pharmacokinetic Trial of Rifabutin with Lopinavir/Ritonavir-Antiretroviral Therapy in Patients with HIV-Associated Tuberculosis in Vietnam
BACKGROUND: Rifampicin and protease inhibitors are difficult to use concomitantly in patients with HIV-associated tuberculosis because of drug-drug interactions. Rifabutin has been proposed as an alternative rifamycin, but there is concern that the current recommended dose is suboptimal. The princip...
Autores principales: | , , , , , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Public Library of Science
2014
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3898920/ https://www.ncbi.nlm.nih.gov/pubmed/24465443 http://dx.doi.org/10.1371/journal.pone.0084866 |
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author | Lan, Nguyen Thi Ngoc Thu, Nguyen Thi Nguyet Barrail-Tran, Aurélie Duc, Nguyen Hong Lan, Nguyen Ngoc Laureillard, Didier Thi Xuan Lien, Truong Borand, Laurence Quillet, Catherine Connolly, Catherine Lagarde, Dominique Pym, Alexander Lienhardt, Christian Dung, Nguyen Huy Taburet, Anne-Marie Harries, Anthony D |
author_facet | Lan, Nguyen Thi Ngoc Thu, Nguyen Thi Nguyet Barrail-Tran, Aurélie Duc, Nguyen Hong Lan, Nguyen Ngoc Laureillard, Didier Thi Xuan Lien, Truong Borand, Laurence Quillet, Catherine Connolly, Catherine Lagarde, Dominique Pym, Alexander Lienhardt, Christian Dung, Nguyen Huy Taburet, Anne-Marie Harries, Anthony D |
author_sort | Lan, Nguyen Thi Ngoc |
collection | PubMed |
description | BACKGROUND: Rifampicin and protease inhibitors are difficult to use concomitantly in patients with HIV-associated tuberculosis because of drug-drug interactions. Rifabutin has been proposed as an alternative rifamycin, but there is concern that the current recommended dose is suboptimal. The principal aim of this study was to compare bioavailability of two doses of rifabutin (150 mg three times per week and 150 mg daily) in patients with HIV-associated tuberculosis who initiated lopinavir/ritonavir-based antiretroviral therapy in Vietnam. Concentrations of lopinavir/ritonavir were also measured. METHODS: This was a randomized, open-label, multi-dose, two-arm, cross-over trial, conducted in Vietnamese adults with HIV-associated tuberculosis in Ho Chi Minh City (Clinical trial registry number NCT00651066). Rifabutin pharmacokinetics were evaluated before and after the introduction of lopinavir/ritonavir -based antiretroviral therapy using patient randomization lists. Serial rifabutin and 25-O-desacetyl rifabutin concentrations were measured during a dose interval after 2 weeks of rifabutin 300 mg daily, after 3 weeks of rifabutin 150 mg daily with lopinavir/ritonavir and after 3 weeks of rifabutin 150 mg three times per week with lopinavir/ritonavir. RESULTS: Sixteen and seventeen patients were respectively randomized to the two arms, and pharmacokinetic analysis carried out in 12 and 13 respectively. Rifabutin 150 mg daily with lopinavir/ritonavir was associated with a 32% mean increase in rifabutin average steady state concentration compared with rifabutin 300 mg alone. In contrast, the rifabutin average steady state concentration decreased by 44% when rifabutin was given at 150 mg three times per week with lopinavir/ritonavir. With both dosing regimens, 2 – 5 fold increases of the 25-O-desacetyl- rifabutin metabolite were observed when rifabutin was given with lopinavir/ritonavir compared with rifabutin alone. The different doses of rifabutin had no significant effect on lopinavir/ritonavir plasma concentrations. CONCLUSIONS: Based on these findings, rifabutin 150 mg daily may be preferred when co-administered with lopinavir/ritonavir in patients with HIV-associated tuberculosis. TRIAL REGISTRATION: ClinicalTrials.gov NCT00651066 |
format | Online Article Text |
id | pubmed-3898920 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2014 |
publisher | Public Library of Science |
record_format | MEDLINE/PubMed |
spelling | pubmed-38989202014-01-24 Randomised Pharmacokinetic Trial of Rifabutin with Lopinavir/Ritonavir-Antiretroviral Therapy in Patients with HIV-Associated Tuberculosis in Vietnam Lan, Nguyen Thi Ngoc Thu, Nguyen Thi Nguyet Barrail-Tran, Aurélie Duc, Nguyen Hong Lan, Nguyen Ngoc Laureillard, Didier Thi Xuan Lien, Truong Borand, Laurence Quillet, Catherine Connolly, Catherine Lagarde, Dominique Pym, Alexander Lienhardt, Christian Dung, Nguyen Huy Taburet, Anne-Marie Harries, Anthony D PLoS One Research Article BACKGROUND: Rifampicin and protease inhibitors are difficult to use concomitantly in patients with HIV-associated tuberculosis because of drug-drug interactions. Rifabutin has been proposed as an alternative rifamycin, but there is concern that the current recommended dose is suboptimal. The principal aim of this study was to compare bioavailability of two doses of rifabutin (150 mg three times per week and 150 mg daily) in patients with HIV-associated tuberculosis who initiated lopinavir/ritonavir-based antiretroviral therapy in Vietnam. Concentrations of lopinavir/ritonavir were also measured. METHODS: This was a randomized, open-label, multi-dose, two-arm, cross-over trial, conducted in Vietnamese adults with HIV-associated tuberculosis in Ho Chi Minh City (Clinical trial registry number NCT00651066). Rifabutin pharmacokinetics were evaluated before and after the introduction of lopinavir/ritonavir -based antiretroviral therapy using patient randomization lists. Serial rifabutin and 25-O-desacetyl rifabutin concentrations were measured during a dose interval after 2 weeks of rifabutin 300 mg daily, after 3 weeks of rifabutin 150 mg daily with lopinavir/ritonavir and after 3 weeks of rifabutin 150 mg three times per week with lopinavir/ritonavir. RESULTS: Sixteen and seventeen patients were respectively randomized to the two arms, and pharmacokinetic analysis carried out in 12 and 13 respectively. Rifabutin 150 mg daily with lopinavir/ritonavir was associated with a 32% mean increase in rifabutin average steady state concentration compared with rifabutin 300 mg alone. In contrast, the rifabutin average steady state concentration decreased by 44% when rifabutin was given at 150 mg three times per week with lopinavir/ritonavir. With both dosing regimens, 2 – 5 fold increases of the 25-O-desacetyl- rifabutin metabolite were observed when rifabutin was given with lopinavir/ritonavir compared with rifabutin alone. The different doses of rifabutin had no significant effect on lopinavir/ritonavir plasma concentrations. CONCLUSIONS: Based on these findings, rifabutin 150 mg daily may be preferred when co-administered with lopinavir/ritonavir in patients with HIV-associated tuberculosis. TRIAL REGISTRATION: ClinicalTrials.gov NCT00651066 Public Library of Science 2014-01-22 /pmc/articles/PMC3898920/ /pubmed/24465443 http://dx.doi.org/10.1371/journal.pone.0084866 Text en © 2014 Lan et al http://creativecommons.org/licenses/by/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are properly credited. |
spellingShingle | Research Article Lan, Nguyen Thi Ngoc Thu, Nguyen Thi Nguyet Barrail-Tran, Aurélie Duc, Nguyen Hong Lan, Nguyen Ngoc Laureillard, Didier Thi Xuan Lien, Truong Borand, Laurence Quillet, Catherine Connolly, Catherine Lagarde, Dominique Pym, Alexander Lienhardt, Christian Dung, Nguyen Huy Taburet, Anne-Marie Harries, Anthony D Randomised Pharmacokinetic Trial of Rifabutin with Lopinavir/Ritonavir-Antiretroviral Therapy in Patients with HIV-Associated Tuberculosis in Vietnam |
title | Randomised Pharmacokinetic Trial of Rifabutin with Lopinavir/Ritonavir-Antiretroviral Therapy in Patients with HIV-Associated Tuberculosis in Vietnam |
title_full | Randomised Pharmacokinetic Trial of Rifabutin with Lopinavir/Ritonavir-Antiretroviral Therapy in Patients with HIV-Associated Tuberculosis in Vietnam |
title_fullStr | Randomised Pharmacokinetic Trial of Rifabutin with Lopinavir/Ritonavir-Antiretroviral Therapy in Patients with HIV-Associated Tuberculosis in Vietnam |
title_full_unstemmed | Randomised Pharmacokinetic Trial of Rifabutin with Lopinavir/Ritonavir-Antiretroviral Therapy in Patients with HIV-Associated Tuberculosis in Vietnam |
title_short | Randomised Pharmacokinetic Trial of Rifabutin with Lopinavir/Ritonavir-Antiretroviral Therapy in Patients with HIV-Associated Tuberculosis in Vietnam |
title_sort | randomised pharmacokinetic trial of rifabutin with lopinavir/ritonavir-antiretroviral therapy in patients with hiv-associated tuberculosis in vietnam |
topic | Research Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3898920/ https://www.ncbi.nlm.nih.gov/pubmed/24465443 http://dx.doi.org/10.1371/journal.pone.0084866 |
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