Publication
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 | 2019-12-16T14:46:41Z | |
| dc.date.available | 2019-12-16T14:46:41Z | |
| dc.date.issued | 2017-10 | |
| 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.version | info:eu-repo/semantics/publishedVersion | pt_PT |
| dc.identifier.citation | Journal of Pharmaceutical Sciences. October 2017, 106(10):3161-3166 | pt_PT |
| dc.identifier.doi | 10.1016/j.xphs.2017.06.004 | pt_PT |
| dc.identifier.issn | 0022-3549 | |
| dc.identifier.uri | http://hdl.handle.net/10400.26/30507 | |
| dc.language.iso | eng | pt_PT |
| dc.peerreviewed | yes | pt_PT |
| dc.publisher | Elsevier | pt_PT |
| dc.relation.publisherversion | https://doi.org/10.1016/j.xphs.2017.06.004 | 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.citation.endPage | 3166 | pt_PT |
| oaire.citation.startPage | 3161 | pt_PT |
| oaire.citation.title | Journal of Pharmaceutical Sciences | pt_PT |
| oaire.citation.volume | 106(10) | pt_PT |
| rcaap.embargofct | Política de copyright do editor | pt_PT |
| rcaap.rights | restrictedAccess | pt_PT |
| rcaap.type | article | pt_PT |