Class-specific relative genetic contribution for key antiretroviral drugs.
J Antimicrob Chemother
; 70(11): 3074-9, 2015 Nov.
Article
en En
| MEDLINE
| ID: mdl-26221018
ABSTRACT
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 1â-â(1â/âF) where Fâ=âSDb(2)â/âSDw(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.
Texto completo:
1
Colección:
01-internacional
Base de datos:
MEDLINE
Asunto principal:
Farmacogenética
/
Plasma
/
Antirretrovirales
Tipo de estudio:
Observational_studies
Límite:
Adult
/
Aged
/
Aged80
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Female
/
Humans
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Male
/
Middle aged
Idioma:
En
Revista:
J Antimicrob Chemother
Año:
2015
Tipo del documento:
Article
País de afiliación:
Reino Unido