Pharmacokinetic and pharmacodynamic evaluation of raltegravir and experience from clinical trials in HIV-positive patients

Abstract

Raltegravir for its tolerability, efficacy, few drug-to-drug interactions and for the amount of available data in difficult subgroups of patients is a key drug in the antiretroviral armamentarium. For its weak genetic barrier to resistance and erratic pharmacokinetic profile, it should be administered twice daily and with fully active companion antiretrovirals.

Impact of UGT1A1 polymorphisms on Raltegravir and its glucuronide plasma concentrations in a cohort of HIV-1 infected patients

“…Consistent with the fact that RAL is generally considered as a well-tolerated drug, we observed very few clinical AE or biological abnormalities 2 , 3 , 24 and, with the exception of the sentiment of fatigue that is an unspecific AE, none of our reported AE or biological abnormalities was correlated with either UGT1A1 polymorphisms or RAL exposure (Fig. 1 ).…”

“…In conclusion, most of the previous studies failed to demonstrate a correlation between RAL plasma exposure and UGT1A1*28 polymorphism. RAL is well known to have erratic pharmacokinetic profile with high intra- and inter- individual variability and coefficients of variations (CV) of 122–245% and 110–212% when considering the plasma concentrations within the same individual or between individuals, respectively 23 , 24 . This high degree of variability observed in the PK behavior of RAL combined with the small sample size of the above-mentioned cohorts 16 – 18 has a potential negative impact on the statistical power and might explain why the UGT1A1*28 allele is not always significantly associated with variations of RAL plasma exposure by hiding the true pharmacogenomic effect of this variant.…”

Relevancia clínica de las interacciones medicamentosas en pacientes infectados con el virus de la inmunodeficiencia humana: actualización 2015-2017

“…Carbonato de calcio 21,41,42,43,44 Hidróxido de aluminio 21,41,42,43,44 Hidróxido de magnesio 21,41,42,43,44 RAL 2: Riesgo alto Los antiácidos pueden producir quelación y disminuir la absorción de RAL y con ello, disminuir sus concentraciones plasmáticas hasta 67%. Administrar con al menos una hora de diferencia entre RAL y los antiácidos…”

“…Fumarato ferroso 21,41,42,43,44,45 Carbonato de calcio 21,41,42,43,44,45 Hidróxido de aluminio 21,41,42,43,44,45 Hidróxido de magnesio 21,41,42,43,44,45 Sofosbuvir 20, 35,59 EFV No hay cambios en la Cp de ledipasvir/sofosbuvir y sofosbuvir con el EFV. No se requiere ajuste en la dosis…”

Raltegravir 1200 mg Once Daily vs 400 mg Twice Daily, With Emtricitabine and Tenofovir Disoproxil Fumarate, for Previously Untreated HIV-1 Infection: Week 96 Results From ONCEMRK, a Randomized, Double-Blind, Noninferiority Trial

“…Raltegravir 400 mg twice daily (BID), the first integrase strand transfer inhibitor (INSTI) approved for the treatment of HIV-1 infection, has a well-established safety and efficacy profile in treatment-naive and treatment-experienced patients. 1 – 4 A once-daily formulation of raltegravir 1200 mg (2 × 600 mg tablets) has been developed and has the potential to improve treatment adherence and satisfy patient preference for a once-daily regimen. 5 – 8 This new formulation is approved for use in combination with other antiretroviral agents for previously untreated HIV-1 infection in adults and in children weighing ≥40 kg.…”