Publicação
Population approach to efavirenz therapy
| dc.contributor.author | Duarte, Hélder | |
| dc.contributor.author | Cruz, João Paulo | |
| dc.contributor.author | Aniceto, Natália | |
| dc.contributor.author | Ribeiro, Ana Clara | |
| dc.contributor.author | Fernandes, Ana | |
| dc.contributor.author | Paixão, Paulo | |
| dc.contributor.author | Antunes, Francisco | |
| dc.contributor.author | Morais, José | |
| dc.date.accessioned | 2019-11-13T17:08:26Z | |
| dc.date.available | 2019-11-13T17:08:26Z | |
| dc.date.issued | 2017 | |
| dc.description | © 2017 American Pharmacists Association®. Published by Elsevier Inc. All rights reserved. | pt_PT |
| dc.description.abstract | Efavirenz (EFV) is a nonnucleoside reverse transcriptase inhibitor commonly used as first-line therapy in the treatment of human immunodeficiency virus (HIV), with a narrow therapeutic range and a high between-subject variability which can lead to central nervous system toxicity or therapeutic failure. To characterize the sources of variability and better predict EFV steady-state plasma concentrations, a population pharmacokinetic model was developed from 96 HIV-positive individuals, using a nonlinear mixed-effect method with Monolix® software. A one-compartment with first-order absorption and elimination model adequately described the data. To explain between-subject variability, demographic characteristics, biochemical parameters, hepatitis C virus–HIV coinfection, and genetic polymorphisms were tested. A combination of the single-nucleotide polymorphisms rs2279343 and rs3745274, both in the CYP2B6 gene, were the only covariates influencing clearance, included in the final model. Oral clearance was estimated to be 19.6 L/h, 14.15 L/h, and 6.08 L/h for wild-type, heterozygous mutated and homozygous mutated individuals, respectively. These results are in accordance with the current knowledge of EFV metabolism and also suggest that in homozygous mutated individuals, a dose adjustment is necessary. Hepatitis C virus–HIV coinfection does not seem to be a predictive indicator of EFV pharmacokinetic disposition. | pt_PT |
| dc.description.sponsorship | This research was partially supported by a grant from Fundação para a Ciência e a Tecnologia (FCT - Foundation for Science and Technology) (PTDC/DTP-FTO/1747/2012) of the Portuguese Ministry of Science. | pt_PT |
| dc.description.version | info:eu-repo/semantics/publishedVersion | pt_PT |
| dc.identifier.citation | Journal of Pharmaceutical Sciences 106 (2017) 3161-3166 | pt_PT |
| dc.identifier.doi | 10.1016/j.xphs.2017.06.004 | |
| dc.identifier.issn | 0022-3549 | |
| dc.identifier.uri | http://hdl.handle.net/10451/40138 | |
| dc.language.iso | eng | pt_PT |
| dc.peerreviewed | yes | pt_PT |
| dc.publisher | Elsevier | pt_PT |
| dc.relation.publisherversion | https://www.jpharmsci.org/ | pt_PT |
| dc.subject | Population pharmacokinetics | pt_PT |
| dc.subject | CYP enzymes | pt_PT |
| dc.subject | HIV/AIDS | pt_PT |
| dc.subject | Therapeutic drug monitoring | pt_PT |
| dc.subject | Pharmacogenetics | pt_PT |
| dc.title | Population approach to efavirenz therapy | pt_PT |
| dc.type | journal article | |
| dspace.entity.type | Publication | |
| oaire.awardNumber | PTDC/DTP-FTO/1747/2012 | |
| oaire.awardURI | info:eu-repo/grantAgreement/FCT/3599-PPCDT/PTDC%2FDTP-FTO%2F1747%2F2012/PT | |
| oaire.citation.endPage | 3166 | pt_PT |
| oaire.citation.issue | 10 | pt_PT |
| oaire.citation.startPage | 3161 | pt_PT |
| oaire.citation.title | Journal of Pharmaceutical Sciences | pt_PT |
| oaire.citation.volume | 106 | pt_PT |
| oaire.fundingStream | 3599-PPCDT | |
| person.familyName | Antunes | |
| person.givenName | Francisco | |
| person.identifier.orcid | 0000-0001-7932-1154 | |
| person.identifier.scopus-author-id | 7006648941 | |
| project.funder.identifier | http://doi.org/10.13039/501100001871 | |
| project.funder.name | Fundação para a Ciência e a Tecnologia | |
| rcaap.rights | restrictedAccess | pt_PT |
| rcaap.type | article | pt_PT |
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