Class-specific relative genetic contribution for key antiretroviral drugs.
Objectives: Antiretroviral pharmacokinetics is defined by numerous factors affecting absorption, distribution, metabolism and elimination. Biological processes underpinning drug distribution are only partially characterized and multiple genetic factors generate cumulative or antagonistic interaction...
| Publicado en: | Journal of Antimicrobial Chemotherapy (JAC) Vol. 70; no. 11; pp. 3074 - 3080 |
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| Autores principales: | , , , , , , , |
| Formato: | research Journal Article |
| Publicado: |
Oxford University Press / USA
Nov2015
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| Acceso en línea: | Ver este registro en EBSCOhost |
| fields | @attributes: recordID: 1 pdfLink: plink: https://search.ebscohost.com/login.aspx?direct=true&db=ccm&AN=110493326&site=ehost-live header: @attributes: shortDbName: ccm uiTerm: 110493326 longDbName: CINAHL Complete uiTag: AN controlInfo: bkinfo: dissinfo: jinfo: jid: 03057453 N5O jtl: Journal of Antimicrobial Chemotherapy (JAC) issn: 03057453 maglogo: N pubinfo: dt: Nov2015 vid: 70 iid: 11 pid: 622 pub: Oxford University Press / USA artinfo: ui: 110493326 110493326 NLM26221018 110493326 10.1093/jac/dkv207 NLM26221018 110493326 ppf: 3074 ppct: 6 formats: tig: atl: Class-specific relative genetic contribution for key antiretroviral drugs. aug: au: Siccardi, Marco Olagunju, Adeniyi Simiele, Marco D'Avolio, Antonio Calcagno, Andrea Di Perri, Giovanni Bonora, Stefano Owen, Andrew affil: Molecular and Clinical Pharmacology, Institute of Translational Medicine, University of Liverpool, Liverpool, UK sug: subj: Plasma Anti-Retroviral Agents Pharmacokinetics Pharmacogenetics Methods Aged, 80 and Over Female Anti-Retroviral Agents Administration and Dosage Middle Age Young Adult Retrospective Design Male Adult Aged Funding Source Human Aged, 80 & over Middle Aged: 45-64 years Adult: 19-44 years Aged: 65+ years Female Male ab: Objectives: Antiretroviral pharmacokinetics is defined by numerous factors affecting absorption, distribution, metabolism and elimination. Biological processes underpinning drug distribution are only partially characterized and multiple genetic factors generate cumulative or antagonistic interactions, which complicates the implementation of pharmacogenetic markers. The aim of this study was to assess the degree to which heredity influences pharmacokinetics through the quantification of the relative genetic contribution (rGC) for key antiretrovirals.Methods: A total of 407 patients receiving lopinavir/ritonavir, atazanavir/ritonavir, atazanavir, efavirenz, nevirapine, etravirine, maraviroc, tenofovir or raltegravir were included. Intra-patient variability (SDw) and inter-patient (SDb) variability were measured in patients with plasma concentrations available from more than two visits. The rGC was calculated using the following equation: 1 - (1 / F) where F = SDb(2) / SDw(2).Results: Mean (95% CI) rGC was calculated to be 0.81 (0.72-0.88) for efavirenz, 0.74 (0.61-0.84) for nevirapine, 0.67 (0.49-0.78) for etravirine, 0.65 (0.41-0.79) for tenofovir, 0.59 (0.38-0.74) for atazanavir, 0.47 (0.27-0.60) for atazanavir/ritonavir, 0.36 (0.01-0.48) for maraviroc, 0.15 (0.01-0.44) for lopinavir/ritonavir and 0 (0-0.33) for raltegravir.Conclusions: The rank order for genetic contribution to variability in plasma concentrations for the study drugs was efavirenz > nevirapine > etravirine > tenofovir > atazanavir > atazanavir/ritonavir > maraviroc > lopinavir/ritonavir > raltegravir, indicating that class-specific differences exist. The rGC strategy represents a useful tool to rationalize future investigations as drugs with higher rGC scores may represent better candidates for pharmacogenetic-pharmacokinetic studies. pubtype: Academic Journal doctype: research Journal Article ougenre: Article language: English refInfo: holdings: @attributes: islocal: N |
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