Once daily maraviroc 300 mg or 150 mg in combination with ritonavir-boosted darunavir 800/100 mg

Abstract

Once daily coadministration of 300 mg of maraviroc with 800/100 mg of darunavir/ritonavir was well tolerated and had favourable pharmacokinetics when compared with 300 mg of maraviroc twice daily with 245 mg of tenofovir/200 mg of emtricitabine. A 24% higher C(trough) and 107% higher C(peak) was seen in black patients compared with white patients.

Use of In Vitro to In Vivo Extrapolation to Predict the Optimal Strategy for Patients Switching from Efavirenz to Maraviroc or Nevirapine

“…The simulated mean maraviroc C trough values were similar to those determined by Waters et al [24], with both experimentally observed and simulated C trough values exceeding the C trough and C avg values of \0.025 and \0.075 mg/L, respectively (concentrations previously associated with near-maximal virological responses) for the wildtype virus [8,27]. The simulated C trough values were slightly higher than the clinically observed data (within a twofold window).…”

“…This strategy showed a decrease in the plasma concentrations during the initial 2 weeks, but they were still above the suggested concentrations required [C trough and average concentration (C avg ) \0.025 and \0.075 mg/L, respectively] for optimal virological response [8,27] (Fig. 2).…”

CYP3A5 Genotype Impacts Maraviroc Concentrations in Healthy Volunteers

“…Maraviroc was approved based on the MOTIVATE trials comprised of 85% individuals with European ancestry (Gulick et al, 2008) and most previous maraviroc pharmacokinetic studies were conducted in participants with European ancestry, with the median percentage of participants with European ancestry at 78.5% (Abel et al, 2008a,b,c,d,f;Chan et al, 2008;Pozniak et al, 2008;Dumond et al, 2009;Andrews et al, 2010;Ramanathan et al, 2010;Brown et al, 2011;Kakuda et al, 2011;Gruber et al, 2013;Mora-Peris et al, 2013;Taiwo et al, 2013;Vourvahis et al, 2013). A few studies compared maraviroc concentrations in individuals with African ancestry with individuals with European ancestry and concluded that there were no differences or higher concentrations in individuals with African ancestry (FDA, 2007;Okoli et al, 2012), which may be due to the use of CYP3A inhibitors such as ritonavir in the optimized background therapy in which CYP3A5 activity may have been inhibited in individuals who are carrying CYP3A5*1 allele. Nevertheless, a recent maraviroc exposure-response relationship assessment suggested that ethnicity is a prognostic factor of virologic success in the final model, with an odds ratio of 0.35 for people with African ancestry versus European ancestry when controlling for other prognostic factors (Jacqmin et al, 2013).…”

Safety, efficacy and indications of prescription of maraviroc in clinical practice: Factors associated with clinical outcomes

“…Approved for twice daily use, maraviroc has been used once-daily in selected individuals based on pharmacokinetic studies and information provided in clinical trials (Okoli et al, 2012;Gulick et al, 2008;Taiwo et al, 2013;Mills et al, 2013;Calcagno et al, 2013;Macias et al, 2014;Stellbrink et al, 2014). More recently, there has been growing interest in NRTI-limiting or -sparing regimens, some of them including maraviroc (Gunthard et al, 2014;Okoli et al, 2012;Taiwo et al, 2013;Mills et al, 2013;Calcagno et al, 2013;Macias et al, 2014;Stellbrink et al, 2014).…”

“…More recently, there has been growing interest in NRTI-limiting or -sparing regimens, some of them including maraviroc (Gunthard et al, 2014;Okoli et al, 2012;Taiwo et al, 2013;Mills et al, 2013;Calcagno et al, 2013;Macias et al, 2014;Stellbrink et al, 2014).…”