Plasma concentrations of maraviroc and raltegravir after dual therapy in patients with long-term suppressed viraemia: ROCnRAL ANRS 157 study.
1. There were satisfactory C max and C min only in Patient 2, whereas in Patient 1 there was an increased CL and reduced AUC. Since the PK/pharmacodynamic parameter of importance for linezolid activity is the AUC/MIC ratio, assessing changes in AUC exposure by body size is of paramount importance. 6 Only Patient 2 had satisfactory values of AUC and AUC/MIC. Furthermore, since linezolid PK is not related to renal function, the creatinine clearance values of .120 and 40 mL/min in Patients 1 and 2, respectively, are not helpful in understanding the alteration of plasma clearance. Moreover, the observation of higher V (141.6 and 80.9 L in Patients 1 and 2, respectively) when compared with healthy volunteers (52 L) confirms the suggestion of a relationship between weight and V in determining a significant decrease of plasma exposure. 7 Taken together, these data suggest that linezolid PK may be strongly influenced by the degree of obesity and standard doses are not sufficient, further noting that linezolid undergoes slow non-enzymatic oxidation mediated by ubiquitous reactive species in vivo. 8 Accordingly, since a higher production of reactive oxygen species was found in adipose tissues of obese mice, it was also hypothesized that linezolid could be highly metabolized in obesity, thus explaining low linezolid concentrations. 9 This is the first known report where the PK targets of linezolid are not achieved even with 'every 8 h' administration and an MIC within the range of susceptibility in morbidly obese patients, which should be considered at risk of underdosing linezolid. According to these data, therapeutic drug monitoring is needed to check if 'every 8 h' or perhaps 'every 6 h' or continuous infusions are required in critically ill obese patients. 4 Canut A, Isla A, Betriu C et al. Pharmacokinetic-pharmacodynamic evaluation of daptomycin, tigecycline, and linezolid versus vancomycin for the treatment of MRSA infections in four western European countries. et al. Clinical pharmacokinetic/pharmacody-namic profile of linezolid in severely ill intensive care unit patients. 7 Muzevich KM, Lee KB. Subtherapeutic linezolid concentrations in a patient with morbid obesity and methicillin-resistant Staphylococcus aureus pneumonia: case report and review of the literature. 9 Furukawa S, Fujita T, Shimabukuro M et al. Increased oxidative stress in obesity and its impact on metabolic syndrome. †Members are listed in the Acknowledgements section. Sir, In a growing population of ageing and polymedicated HIV-infected patients, long-term tolerance remains a major public health issue. Current …