Urological complaints in relation to indinavir plasma concentrations in HIV-infected patients

Objective: To assess the relationship between indinavir-associated urologic al complaints and indinavir plasma concentrations. Design: Case series, comparing indinavir plasma concentrations in cases wit h average concentrations in a control group. Methods: Patients taking 800 mg indinavir three times a day (tid), who pres ented with overt urological complaints (renal colic, flank pain or haematur ia) were selected for the study. Plasma indinavir concentrations were measu red by means of a standardized high performance liquid chromatography (HPLC ) method. Plasma samples taken at 1.5-8 h after the last indinavir ingestio n were included for evaluation. Results were compared with the full pharmac okinetic curves of indinavir plasma concentrations from a control group of 14 patients taking 800 mg indinavir rid without urological complaints, and were expressed as concentration ratios. A ratio of 1 indicated a plasma con centration 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 co ncentrations of 15 patients could be evaluated. Fourteen (93%) patients had a concentration above the mean of the controls, 12 (80%) patients had a co ncentration above the upper 95% confidence limit, and one (7%) patient had a concentration below the lower 95% confidence limit. The mean indinavir co ncentration 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 co ncentrations 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 vira l loads of less than 500 copies per mi 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 pat ients in this study. Indinavir plasma concentrations should be monitored up on presentation of urological complaints, on the basis of which dose reduct ions may be applied if brief interruption and increased hydration are ineff ective. (C) 1999 Lippincott Williams & Wilkins.