Clinical pharmacokinetics of antiretroviral drugs in older persons

Expert Opin Drug Metab Toxicol. 2013 May;9(5):573-88. doi: 10.1517/17425255.2013.781153. Epub 2013 Mar 20.

Abstract

Introduction: Combination antiretroviral therapy has enabled HIV-infected persons to reach older ages in high numbers. Hepatic and renal changes that normally occur with advancing age occur earlier and with higher incidence in HIV-infected individuals. A limited number of prospective controlled studies have demonstrated small reductions (17 to 41%) in lopinavir, atazanavir and lamivudine clearance in older versus younger adults. A much larger number of retrospective studies in adults (age range ∼ 20 to 60 years), including all antiretroviral drugs, have evaluated age as a covariate for pharmacokinetics. Most studies did not detect substantial associations between drug exposures and age.

Areas covered: This review summarizes antiretroviral drug pharmacokinetics in older persons. The authors review articles from PubMed (search terms: elderly, antiretroviral, pharmacokinetics) in addition to the bibliographies of those selected.

Expert opinion: The evidence to date does not support major pharmacokinetic changes in adults between ∼ 20 and 60 years of age. However, additional prospective, well-controlled studies are needed in more persons > 60 years, including those with frailty and comorbidities, with assessment of unbound drug clearance, and incorporation of adherence, pharmacogenetics and concomitant medications. Until then, guidelines for drug-drug interactions and dosing in renal and hepatic impairment should be followed in older HIV-infected individuals.

Publication types

  • Research Support, N.I.H., Extramural
  • Review

MeSH terms

  • Adult
  • Aged
  • Anti-HIV Agents / pharmacokinetics*
  • Anti-HIV Agents / therapeutic use
  • Atazanavir Sulfate
  • Dose-Response Relationship, Drug
  • Drug Interactions
  • Guidelines as Topic
  • HIV Infections / drug therapy*
  • HIV Protease Inhibitors / pharmacokinetics
  • HIV Protease Inhibitors / therapeutic use
  • Humans
  • Kidney / drug effects
  • Kidney / metabolism
  • Lamivudine / pharmacokinetics*
  • Lamivudine / therapeutic use
  • Liver / drug effects
  • Liver / metabolism
  • Lopinavir / pharmacokinetics*
  • Lopinavir / therapeutic use
  • Middle Aged
  • Oligopeptides / pharmacokinetics*
  • Oligopeptides / therapeutic use
  • Pyridines / pharmacokinetics*
  • Pyridines / therapeutic use
  • Young Adult

Substances

  • Anti-HIV Agents
  • HIV Protease Inhibitors
  • Oligopeptides
  • Pyridines
  • Lopinavir
  • Lamivudine
  • Atazanavir Sulfate