title: Role of therapeutic drug monitoring for protease inhibitors.
abstract: OBJECTIVE
  To review the role of therapeutic drug monitoring (TDM) for protease inhibitors in the treatment of HIV infection.
  
  
  METHODS
  Primary articles were identified using MEDLINE (1966-October 2000), EMBASE (1987-October 2000), AIDSLINE (1980-October 2000), Current Contents, PubMed, and Medscape. Further articles were identified from bibliographic review of primary articles and review papers. Abstracts presented at the World AIDS Conference, Interscience Conference on Antimicrobial Agents and Chemotherapy, and Conference on Retroviruses and Opportunistic Infections were also identified from 1997 to 2000.
  
  
  METHODS
  All English-language, prospective clinical trials, as well as selected retrospective studies and case series, pertaining to therapeutic drug monitoring of protease inhibitors were included.
  
  
  RESULTS
  A number of clinical studies have found a good relationship between concentration and pharmacologic response and/or toxicity as well as wide interpatient variability in the pharmacokinetics of protease inhibitors. There also is some preliminary evidence of the usefulness of plasma drug concentrations to guide dosage adjustments of protease inhibitors in patients with liver dysfunction. Furthermore, there is preliminary evidence of a relationship between drug concentrations and resistance.
  
  
  CONCLUSIONS
  A number of clinical studies support the usefulness of TDM of protease inhibitors. However, before TDM can be of the most value, further evaluation requires simplified and standardized assays to be performed routinely by clinical laboratories; determination of the appropriate target concentration and therapeutic range, as well as the best predictor of pharmacologic response; and refined interpretation of plasma drug concentrations. Randomized, controlled clinical trials of patient outcomes are needed to assess the clinical utility of TDM for protease inhibitors.
authors.affiliation: Faculty of Pharmaceutical Sciences, University of British Columbia, Vancouver, British Columbia, Canada.
authors.forename: L
authors.initials: L
authors.lastname: John
authors.forename: F
authors.initials: F
authors.lastname: Marra
authors.forename: M H
authors.initials: MH
authors.lastname: Ensom
mesh_terms: D002986:Clinical Trials as Topic; D016903:Drug Monitoring; D004351:Drug Resistance; D004357:Drug Synergism; D015658:HIV Infections / Q000188:drug therapy*; D017320:HIV Protease Inhibitors / Q000009:adverse effects / Q000493:pharmacokinetics / Q000627:therapeutic use*; D006801:Humans; D010349:Patient Compliance; D016896:Treatment Outcome
chemical_list: D017320:HIV Protease Inhibitors