title: The pharmacokinetics of HIV protease inhibitor combinations.
abstract: OBJECTIVE
  The clinical use of double-boosted protease inhibitor regimens has evolved recently. This strategy offers a number of unique benefits, including pharmacokinetic enhancement of two different protease inhibitors with low dose ritonavir. We review the pharmacologic rationale for the double-boosted protease inhibitor combinations and the complex drug-drug interactions that occur among different protease inhibitors when co-administered.
  
  
  RESULTS
  The discovery and widespread clinical use of low dose ritonavir as a pharmacoenhancer of other protease inhibitors has significantly improved the management of HIV infection treatment. This has subsequently led to the development of double-boosted protease inhibitor regimens which have been shown to be effective in heavily pre-treated patients, in whom it is crucial to maintain drug concentrations sufficient to suppress viruses with multiple resistance mutations. Interesting pharmacokinetic data have been recently produced showing the complexity of the interactions among three protease inhibitors. As the outcome of these multidrug interactions may be difficult to predict, formal pharmacokinetic studies have been fundamental to determine which protease inhibitors are best to administer in combination.
  
  
  CONCLUSIONS
  This review summarizes the current literature regarding the pharmacokinetics of double-boosted protease inhibitor regimens and general considerations regarding their usage in the treatment of HIV-infected patients.
authors.affiliation: PK Research, Chelsea and Westminster Hospital, London, UK. marta.boffito@chelwest.nhs.uk
authors.forename: Marta
authors.initials: M
authors.lastname: Boffito
authors.forename: Desmond
authors.initials: D
authors.lastname: Maitland
authors.forename: Yohan
authors.initials: Y
authors.lastname: Samarasinghe
authors.forename: Anton
authors.initials: A
authors.lastname: Pozniak
mesh_terms: D004359:Drug Therapy, Combination; D015658:HIV Infections / Q000188:drug therapy; D017320:HIV Protease Inhibitors / Q000008:administration & dosage / Q000493:pharmacokinetics*; D006801:Humans
chemical_list: D017320:HIV Protease Inhibitors