title: Therapeutic drug monitoring of indinavir in HIV-infected patients undergoing HAART.
abstract: BACKGROUND
  Therapeutic drug monitoring (TDM) of protease inhibitors (PI) is gaining increasing importance for the management of HIV-infected patients undergoing highly active antiretroviral therapy (HAART). The PI indinavir (IDV) is widely used in HAART regimens. Combinations of IDV with ritonavir (RTV) have been used to increase the plasma concentration of IDV. However, the desirable IDV concentration range in clinical practice remains to be elucidated.
  
  
  METHODS
  To study the value of TDM for IDV in clinical practice, a retrospective analysis of 501 plasma samples of patients treated with IDV in various dosages was performed. IDV levels were determined during routine outpatient visits. Analysis was performed by high pressure liquid chromatography (HPlC) with UV detection.
  
  
  RESULTS
  A widespread range of IDV plasma concentrations was seen both within and between patients. The mean IDV level during therapy with IDV 2.4 g/d was 3,260 ng/ml (95% CI: 2,903 ng/ml; 3,618 ng/ml). IDV levels at a dose of IDV 1.6 g/d in combination with RTV resulted in a mean IDV plasma concentration of 4,191 ng/ml (95% CI: 3,356 ng/ml; 5,026 ng/ml). There was no significant difference between plasma levels at the doses of 2.4 g/d and 1.6 g/d. 35 of all 130 patients treated with IDV reached only suboptimal IDV plasma concentrations below the limit of 150 ng/ml. There was no statistically significant difference between the number of patients below an IDV plasma concentration of 150 ng/ml in the various dosage regimens.
  
  
  CONCLUSIONS
  During therapy with IDV in a b.i.d. scheme, similar IDV plasma concentrations and a comparable number of patients with subinhibitory plasma concentrations were observed when compared to a therapeutic regimen with t.i.d. dosing. In this study, even at various times of plasma sampling after oral ingestion, TCM facilitated the surveillance of patients compliance.
authors.affiliation: Dept of Hepatology and Infectious Disease, Medical Policlinic, University of Würzburg, Germany. p.langmann@medizin-uni.wuerzburg.de
authors.forename: P
authors.initials: P
authors.lastname: Langmann
authors.forename: M
authors.initials: M
authors.lastname: Zilly
authors.forename: B
authors.initials: B
authors.lastname: Weissbrich
authors.forename: S
authors.initials: S
authors.lastname: Desch
authors.forename: T
authors.initials: T
authors.lastname: Väth
authors.forename: H
authors.initials: H
authors.lastname: Klinker
mesh_terms: D023241:Antiretroviral Therapy, Highly Active; D002851:Chromatography, High Pressure Liquid; D016903:Drug Monitoring; D015658:HIV Infections / Q000188:drug therapy*; D017320:HIV Protease Inhibitors / Q000008:administration & dosage / Q000097:blood* / Q000627:therapeutic use; D015497:HIV-1; D006801:Humans; D019469:Indinavir / Q000008:administration & dosage / Q000097:blood* / Q000627:therapeutic use; D010349:Patient Compliance; D012189:Retrospective Studies; D019438:Ritonavir / Q000008:administration & dosage / Q000627:therapeutic use
chemical_list: D017320:HIV Protease Inhibitors; D019469:Indinavir; D019438:Ritonavir