ABSTRACT
Retrospective studies have documented a significant association between linezolid (LNZ) plasma concentrations and drug-related haematological toxicity. However, the safe upper threshold level for LNZ plasma trough concentrations (Cmin values) has not been defined with certainty. A prospective observational study was performed aimed at comparing LNZ Cmin values in patients developing drug-related side effects with those measured in patients not experiencing LNZ toxicity. LNZ Cmin values were measured from the first week after starting therapy and were repeated periodically up to the end of treatment. Fifty patients, for a total of 210 LNZ Cmin evaluations, were considered. All patients (n=9) who developed drug-related haematological toxicity also had significantly higher plasma LNZ Cmin values during the first week of therapy (9.0±6.4 mg/L vs. 4.9±3.7 mg/L; P<0.01) and thereafter (9.3±5.4 mg/L vs. 4.4±3.4 mg/L; P<0.01). The significant association between LNZ plasma concentrations and haematological toxicity was also confirmed by multivariate logistic regression analysis including age, serum creatinine and concomitant medications as independent variables. A causal relationship between LNZ concentrations and the risk of developing drug-related haematological toxicity was observed. Accordingly, application of therapeutic drug monitoring may improve the safety outcome of patients receiving LNZ therapy.
Subject(s)
Acetamides/adverse effects , Acetamides/pharmacokinetics , Anti-Bacterial Agents/adverse effects , Anti-Bacterial Agents/pharmacokinetics , Blood Cells/drug effects , Gram-Positive Bacterial Infections/drug therapy , Oxazolidinones/adverse effects , Oxazolidinones/pharmacokinetics , Plasma/chemistry , Acetamides/administration & dosage , Adult , Aged , Aged, 80 and over , Anti-Bacterial Agents/administration & dosage , Drug Monitoring , Female , Humans , Linezolid , Male , Middle Aged , Oxazolidinones/administration & dosage , Prospective Studies , Risk AssessmentSubject(s)
Anti-HIV Agents/therapeutic use , Antiretroviral Therapy, Highly Active , HIV Infections/drug therapy , Age Factors , Anti-HIV Agents/administration & dosage , Anti-HIV Agents/adverse effects , Antiretroviral Therapy, Highly Active/adverse effects , Confidence Intervals , Humans , Middle Aged , Odds Ratio , Time Factors , Viral Load/drug effectsABSTRACT
PURPOSE: This study set out to describe the frequency of lipodystrophy, and identify its risk factors, in HIV-positive patients treated with HAART containing at least one protease inhibitor (PI). We analyzed the data collected in the CISAI study. METHODS: The CISAI is a multicenter cohort study that has enrolled 1480 patients. We assessed whether patients had lipodystrophy at a medical visit, with follow-up visits by the same physician at least every 2 months, and also on the basis of patients' own reports. RESULTS: The lipodystrophy syndrome was detected in about 25% of the patients. Multivariate analysis showed the risk of lipodystrophy was correlated with female sex (RR 1.5; 95% confidence interval, CI, 1.2-2.1), with older age, with homosexuality (RR 1.5; 95% CI 1.0-2.4), with overt disease (RR 1.4; 95% CI 1.1-1.8) and with the duration of treatment before entering this study. The RR for ritonavir was higher than for the other PI (RR 1.4; 95% CI 0.9-1.9). Among patients receiving concomitant antiretroviral therapy the risk of lipodystrophy was greater with stavudine (RR 1.7; 95% CI 1.3-2.3). CONCLUSIONS: The study confirmed the high frequency of the lipodystrophy syndrome among patients treated with PI.
