title: Urological complaints in relation to indinavir plasma concentrations in HIV-infected patients.
abstract: OBJECTIVE
  To assess the relationship between indinavir-associated urological complaints and indinavir plasma concentrations.
  
  
  METHODS
  Case series, comparing indinavir plasma concentrations in cases with average concentrations in a control group.
  
  
  METHODS
  Patients taking 800 mg indinavir three times a day (tid), who presented with overt urological complaints (renal colic, flank pain or haematuria) were selected for the study. Plasma indinavir concentrations were measured by means of a standardized high performance liquid chromatography (HPLC) method. Plasma samples taken at 1.5-8 h after the last indinavir ingestion were included for evaluation. Results were compared with the full pharmacokinetic curves of indinavir plasma concentrations from a control group of 14 patients taking 800 mg indinavir tid without urological complaints, and were expressed as concentration ratios. A ratio of 1 indicated a plasma concentration equalling the average concentration in the control population at the same point in time after the ingestion of indinavir.
  
  
  RESULTS
  Seventeen patients (five women) were enrolled and the indinavir concentrations of 15 patients could be evaluated. Fourteen (93%) patients had a concentration above the mean of the controls, 12 (80%) patients had a concentration above the upper 95% confidence limit, and one (7%) patient had a concentration below the lower 95% confidence limit. The mean indinavir concentration in patients with urological complaints (ratio range 0.55-11.49) was significantly higher than the average concentration and the upper 95% confidence limit of the control group (P < 0.05). The results could not be explained by differences in weight, sex or drug interactions. Two patients had chronic active hepatitis B infection. In six patients with indinavir concentrations above the upper 95% limit, indinavir was reduced to 600 mg tid. Upon repeat measurement after the dose adjustment, their indinavir plasma concentrations fell within the 95% confidence interval around the mean of the control population. All six patients remained asymptomatic and had viral loads of less than 500 copies per ml after a follow-up of 5-16 months.
  
  
  CONCLUSIONS
  Urological complications occurring during indinavir treatment were associated with elevated indinavir plasma concentrations in 80% of patients in this study. Indinavir plasma concentrations should be monitored upon presentation of urological complaints, on the basis of which dose reductions may be applied if brief interruption and increased hydration are ineffective.
authors: Department of Internal Medicine, Erasmus University Medical School, Rotterdam, The Netherlands.
authors: J P
authors: JP
authors: Dieleman
authors: I C
authors: IC
authors: Gyssens
authors: M E
authors: ME
authors: van der Ende
authors: S
authors: S
authors: de Marie
authors: D M
authors: DM
authors: Burger
mesh_terms: D000328:Adult; D019380:Anti-HIV Agents / Q000009:adverse effects* / Q000097:blood / Q000493:pharmacokinetics; D005260:Female; D015658:HIV Infections / Q000150:complications* / Q000188:drug therapy / Q000821:virology; D017320:HIV Protease Inhibitors / Q000009:adverse effects* / Q000097:blood / Q000493:pharmacokinetics; D015497:HIV-1; D006801:Humans; D019469:Indinavir / Q000009:adverse effects* / Q000097:blood / Q000493:pharmacokinetics; D008297:Male; D008875:Middle Aged; D014570:Urologic Diseases / Q000139:chemically induced*; D019562:Viral Load
chemical_list: D019380:Anti-HIV Agents; D017320:HIV Protease Inhibitors; D019469:Indinavir