Pharmacokinetic interactions between cobicistat-boosted elvitegravir and darunavir in HIV-infected patients

J Antimicrob Chemother. 2017 Mar 1;72(3):816-819. doi: 10.1093/jac/dkw487.

Abstract

Objectives: To evaluate if there are significant drug-drug interactions between cobicistat-boosted elvitegravir and 800 mg darunavir once daily taken simultaneously, as has been suggested previously.

Methods: The study population consisted of three groups of unselected volunteers taking a regimen of elvitegravir, cobicistat, emtricitabine and tenofovir disoproxil fumarate (150, 150, 200 and 300 mg, respectively) co-formulated in a single tablet plus 800 mg darunavir (group A); only co-formulated elvitegravir, cobicistat, emtricitabine and tenofovir disoproxil fumarate (group B); and cobicistat-boosted darunavir (800 mg darunavir + 150 mg cobicistat) plus two nucleos(t)ide analogues (group C). Elvitegravir, cobicistat and darunavir concentrations at the end of the dosing interval ( C 24 ) were quantified using a validated LC with tandem MS method.

Results: A total of 170 samples were obtained from 24, 32 and 32 patients in groups A, B and C, respectively. In group A, the elvitegravir C 24 were similar to those in group B (233.67 versus 250.39 ng/mL) ( P = 0.406) and the darunavir C 24 were similar to those in group C (1293.54 versus 1319.34 ng/mL) ( P = 0.908). The cobicistat C 24 were comparable in groups A and B (20.2 versus 20.9 ng/mL) and slightly higher in group C (27.7 ng/mL) ( P = 0.059).

Conclusions: The results provide evidence of similar elvitegravir and darunavir C 24 concentrations when these drugs are co-administered as co-formulated elvitegravir, cobicistat, emtricitabine and tenofovir disoproxil fumarate plus 800 mg darunavir or dosed separately.

MeSH terms

  • Adult
  • Aged
  • Aged, 80 and over
  • Anti-HIV Agents / administration & dosage
  • Anti-HIV Agents / pharmacokinetics*
  • Anti-HIV Agents / therapeutic use
  • Cobicistat / administration & dosage*
  • Cobicistat / therapeutic use
  • Darunavir / administration & dosage
  • Darunavir / pharmacokinetics*
  • Darunavir / therapeutic use
  • Drug Combinations
  • Drug Interactions
  • Female
  • HIV Infections / drug therapy*
  • HIV Infections / virology
  • HIV-1 / drug effects
  • Humans
  • Male
  • Middle Aged
  • Quinolones / administration & dosage
  • Quinolones / pharmacokinetics*
  • Quinolones / therapeutic use
  • Young Adult

Substances

  • Anti-HIV Agents
  • Drug Combinations
  • Quinolones
  • elvitegravir
  • Cobicistat
  • Darunavir