The objective of the present retrospective observational study carried out in patients receiving a standard dosage of linezolid and undergoing routine therapeutic drug monitoring (TDM) was to assess the interindividual variability in plasma exposure to identify the prevalence Thiazovivin of attainment of optimal pharmacodynamics and to define if an intensive program of TDM may be warranted in some categories of patients. version 3.1. RESULTS Patient characteristics are shown in Table ?Table1.1. The most frequent hospital admission was surgical (43.5%) and the main reasons for linezolid therapy were bloodstream infections (19.6%) and central nervous system infections (19.6%). TABLE 1. Patient characteristics= 223). For linezolid trough levels sorted relating to individuals’ hospital admissions (Fig. ?(Fig.4) 4 medians (IQ ranges) of is the quantity of observations on each day of treatment. The dashed … When individuals with potential overexposure were compared with those having trough levels within the lower range (<10 mg/liter) normalized daily doses per kg of body weight and route of administration of linezolid were similar (Table ?(Table2).2). However a significantly higher proportion of the individuals with linezolid < 0.001) amiodarone (21.2 versus 2.4% < 0.001) or amlodipine (21.2 versus 5.2 < 0.003). TABLE 2. Assessment of linezolid dosages administration routes and most frequent drug cotreatments in instances with trough levels (Cmin) of ≥10 mg/liter versus those with trough levels of <10 mg/liter Conversation Our findings suggest that during routine clinical use linezolid exposure after standard fixed daily dosages may vary among individuals irrespective of the type of ward of admission. Indeed although median ideals for Cmin Cmaximum and AUC24 were much like those observed in healthy volunteers (17 32 their ranges were significantly wider. From this perspective it would be of interest to clarify if some patient characteristics pathophysiological conditions and/or drug cotreatments might account for this variability. Indeed in our study neither estimated CLCR nor body weight was found to be a useful predictor of linezolid exposure. The absence of a significant relationship between linezolid Cmin and estimated CLCR is attributable to the primarily nonrenal clearance of linezolid (32). This getting allows us to confirm that no major dosage adjustments need to be recommended in individuals with impaired renal function. Similarly linezolid Cmin did not show a definite relationship with individuals’ body weight. In our study very low drug exposures in terms of Cmin Cmaximum and AUC24 among obese individuals were observed only in some cases actually if the limited quantity of instances of TDM carried out with this subpopulation did not enable any certain conclusion. Indeed we notice that linezolid pharmacokinetics may be affected Thiazovivin by the degree of obesity but considering that existing data for this patient demographic are quite sparse and variable (11 19 no empirical alterations of linezolid dose in obese individuals can be suggested to day (19). Overall these observations and the wide interpatient variability seen in this study suggest that it would be hard to accurately forecast the pharmacokinetic disposition of linezolid in all individuals so that the software of TDM at least in some cases seems logical. The good linear relationship between Cmin and estimated AUC24 (r2 = 0.85) suggests that Cmin may represent a useful predictor of Thiazovivin linezolid total body exposure in daily clinical practice. Interestingly our hypothesis is in agreement with a recent population pharmacokinetic study carried out in individuals with MDR tuberculosis treated Rabbit polyclonal to DPYSL3. with linezolid which showed the estimation of AUC based on a trough concentration did not differ significantly from that based on multiple samples (3). Accordingly it may be speculated that TDM of Cmin could be used to guide dosage adjustment with linezolid in individual individuals with the intention of avoiding Thiazovivin either the risk of toxicity or that of restorative failure. Inside a pharmacodynamic study with linezolid it was shown that the two parameters most strongly associated with linezolid effectiveness were Thiazovivin AUC/MIC ratios of >80 to 100 and %TMIC of Thiazovivin 85 (28). Additionally it has been postulated that a Cmin higher than the MIC may be especially useful for linezolid.