Risk factors contributing to a low darunavir plasma concentration

Br J Clin Pharmacol. 2018 Mar;84(3):456-461. doi: 10.1111/bcp.13464. Epub 2017 Dec 7.

Abstract

Darunavir is an efficacious drug; however, pharmacokinetic variability has been reported. The objective of this study was to find predisposing factors for low darunavir plasma concentrations in patients starting the once- or twice-daily dosage. Darunavir plasma concentrations from January 2010 till December 2014 of human immunodeficiency virus-infected individuals treated in the outpatient clinic of the University Medical Center Groningen were retrospectively reviewed. The first darunavir plasma concentration of patients within 8 weeks after initiation of darunavir therapy was selected. A dichotomous logistic regression analysis was conducted to select the set of variables best predicting a darunavir concentration below median population pharmacokinetic curve. In total 113 patients were included. The variables best predicting a darunavir concentration besides food intake included age together with estimated glomerular filtration rate (Hosmer-Lemeshow test P = 0.945, Nagelkerke R2 = 0.284). Systematic evaluation of therapeutic drug monitoring results may help to identify patients at risk for low drug exposure.

Keywords: HIV/AIDS < infectious diseases; antiretrovirals < infectious diseases; patient safety < clinical pharmacology; pharmacokinetics.

MeSH terms

  • Adult
  • Aged
  • Darunavir / administration & dosage*
  • Darunavir / pharmacokinetics
  • Drug Monitoring / methods*
  • Female
  • Food-Drug Interactions
  • Glomerular Filtration Rate / physiology
  • HIV Infections / drug therapy*
  • HIV Protease Inhibitors / administration & dosage*
  • HIV Protease Inhibitors / pharmacokinetics
  • Humans
  • Logistic Models
  • Male
  • Middle Aged
  • Retrospective Studies
  • Risk Factors
  • Young Adult

Substances

  • HIV Protease Inhibitors
  • Darunavir