
doi: 10.1002/jcph.657
pmid: 26449283
AbstractElvitegravir (EVG) is an HIV strand transfer integrase inhibitor approved for the treatment of HIV infection as a part of antiretroviral regimens containing cobicistat (COBI) or ritonavir (RTV) as a booster. The population pharmacokinetics of EVG in treatment‐naive and ‐experienced HIV patients was determined, and the effects of demographic, biometric, and formulation covariates on EVG pharmacokinetics (PK) were evaluated. Data from 31 clinical studies (25 in healthy subjects, 6 phase 1b to phase 3 in HIV‐1–infected patients) with COBI‐boosted EVG studies (as EVG/co or EVG/COBI/FTC/TDF single‐tablet regimen) or RTV‐boosted EVG studies (EVG/r) were analyzed using NONMEM. The effect of the covariates age, sex, race, health status (healthy volunteers vs HIV patients), weight, body mass index (BMI), body surface area (BSA), creatinine clearance (estimated GFR), and formulation were evaluated. EVG PK, with COBI or RTV, was described by a 2‐compartment model, with first‐order absorption and elimination and an absorption lag time. A statistically significant, but not clinically relevant, effect of BSA on EVG clearance (CL) was observed. Coadministration of atazanavir or lopinavir with EVG/r had an effect on EVG CL consistent with the known interaction with these agents. No other covariate had a meaningful effect on EVG PK. EVG PK was well described in a population PK model with HIV‐infected patients, with low PK variability and no relevant effect of demographic or biometric covariates.
Adult, Male, Adolescent, Anti-HIV Agents, HIV Infections, HIV Integrase, Middle Aged, Quinolones, Young Adult, Humans, Drug Therapy, Combination, Female, HIV Integrase Inhibitors, Child, Aged
Adult, Male, Adolescent, Anti-HIV Agents, HIV Infections, HIV Integrase, Middle Aged, Quinolones, Young Adult, Humans, Drug Therapy, Combination, Female, HIV Integrase Inhibitors, Child, Aged
| selected citations These citations are derived from selected sources. This is an alternative to the "Influence" indicator, which also reflects the overall/total impact of an article in the research community at large, based on the underlying citation network (diachronically). | 7 | |
| popularity This indicator reflects the "current" impact/attention (the "hype") of an article in the research community at large, based on the underlying citation network. | Average | |
| influence This indicator reflects the overall/total impact of an article in the research community at large, based on the underlying citation network (diachronically). | Average | |
| impulse This indicator reflects the initial momentum of an article directly after its publication, based on the underlying citation network. | Average |
